Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 16 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1-6 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

ESTRO-HERO survey: Radiotherapy equipment and departments in the European countries: Final results from the ESTRO-HERO survey

Background: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. Methods: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 2629), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). Results: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.31.5) and 1.4 (range 0.44.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCToption). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. Conclusions: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT)

ESTRO-HERO survey: Guidelines for equipment and staffing of radiotherapy facilities in the European countries: Final results of the ESTRO-HERO survey

Background and purpose: In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe. Materials and methods: An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses. Results: The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating. Conclusion: The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need

ESTRO-HERO survey: Radiotherapy staffing in the European countries: Final results from the ESTRO-HERO survey

Background: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. Materials and methods: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 4760), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). Results: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.530.9) for radiation oncologists, 7.6 (019.7) for medical physicists, 3.5 (012.6) for dosimetrists, 26.6 (1.978) for RTTs and 14.8 (0.461.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85757.7) and RTT and nurses 76.8 (range: 25.7156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. Conclusions: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes

Simulación Monte Carlo de las dosis en tumores de pulmón en tratamientos de radioterapia estereotáxica extracraneal

Estudio elaborado a partir de una estancia en el Karolinska University Hospital, Suecia, entre marzo y junio del 2006. En la radioterapia estereotáxica extracraneal (SBRT) de tumores de pulmón existen principalmente dos problemas en el cálculo de la dosis con los sistemas de planificación disponibles: la precisión limitada de los algoritmos de cálculo en presencia de tejidos con densidades muy diferentes y los movimientos debidos a la respiración del paciente durante el tratamiento. El objetivo de este trabajo ha sido llevar a cabo la simulación con el código Monte Carlo PENELOPE de la distribución de dosis en tumores de pulmón en casos representativos de tratamientos con SBRT teniendo en cuenta los movimientos respiratorios y su comparación con los resultados de varios planificadores. Se han estudiado casos representativos de tratamientos de SBRT en el Karolinska University Hospital. Los haces de radiación se han simulado mediante el código PENELOPE y se han usado para la obtención de los resultados MC de perfiles de dosis. Los resultados obtenidos para el caso estático (sin movimiento respiratorio ) ponen de manifiesto que, en comparación con la MC, la dosis (Gy/MU) calculada por los planificadores en el tumor tiene una precisión del 2-3%. En la zona de interfase entre tumor y tejido pulmonar los planificadores basados en el algoritmo PB sobrestiman la dosis en un 10%, mientras que el algoritmo CC la subestima en un 3-4%. Los resultados de la simulación mediante MC de los movimientos respiratorios indican que los resultados de los planificadores son suficientemente precisos en el tumor, aunque en la interfase hay una mayor subestimación de la dosis en comparación con el caso estático. Estos resultados son compatibles con la experiencia clínica adquirida durante 15 años en el Karolinska University Hospital. Los resultados se han publicado en la revista Acta Oncologica.

Technological innovation in creative clusters. The case of laser in conservation of artworks in Florence

The field of laser application to the restoration and cleaning of cultural assets is amongst the most thriving developments of recent times. Ablative laser technological systems are able to clean and protect inestimable works of art subject to atmospheric agents and degradation over time. This new technology, which has been developing for the last forty year, is now available to restorers and has received a significant success all over Europe. An important contribution in the process of laser innovation has been carried out in Florence by local actors belonging to a creative cluster. The objects of the analysis are the genesis of this innovation in this local Florentine context, and the relationships among the main actors who have contributed in it. The study investigates how culture can play a part in the generation of ideas and innovations, and which are the creative environments that can favour it. In this context, the issue of laser technologies for the restoration of cultural heritage has been analysed as a case study in the various paths taken by the Creative Capacity of the Culture (CCC).

Valor pronóstico de la densidad microvascular y de la expresión del VEGF, EGFR y HIF-1 en pacientes con cáncer de cérvix localmente avanzado tratados con quimioradiación

Introducción: Colombia cuenta con poca información sobre el comportamiento del cáncer, no obstante, el carcinoma de cuello uterino representa la segunda causa de muerte por la enfermedad entre las mujeres de nuestro entorno. El patrón epidemiológico de la enfermedad es preocupante porque los estados localmente avanzados constituyen el estado más frecuente al momento del diagnóstico y la mortalidad siendo bastante alta a pesar de la presencia de un programa de cribado organizado. Objetivo: Describir el valor pronóstico de la densidad microvascular (DMV) y de la expresión proteica de varios genes relacionados con la supervivencia y proliferación del cáncer de cérvix localmente avanzado en un grupo de mujeres tratadas con quimioradiación y braquiterapia intracavitaria. Se estimaron la tasa de respuesta global (TRG), la supervivencia libre de progresión (SLP) y la supervivencia global (SG). Resultados: Se incluyeron 61 mujeres con una edad media de 52 ± 10 años; todas tenían diagnóstico de cáncer de cérvix localmente avanzado (IIA 2.3%/IIB 47.5%/IIIA 4.9%/IIIB 37.7%/IVA 3.3%/no definido 3.3%), con un volumen tumoral promedio de 6.4cm (DE ± 1.8cm) e infección por VPH en 46% de los casos; 58 sujetos (95%) tenían un patrón escamoso, dos fueron adenocarcinomas y &50% presentaba neoplasias moderada o pobremente diferenciadas. Todas fueron tratadas con quimioradiación (interrupción transitoria en teleterapia por toxicidad y otras causas en 19% y 21.4%, respectivamente/media de ciclos de platino concomitante 4.8 series ± 1.0) y braquiterapia (77% completaron el tratamiento intracavitario). La mediana para la SLP y global fue de 6.6 meses (r, 4.0-9.1) y 30 meses (r, 11-48), respectivamente. Ninguna de las variables tuvo un efecto positivo sobre la SLP, mientras el análisis multivariado demostró que los niveles de expresión del VEGF (P=0.026), EGFR (P=0.030), y el volumen tumoral menor de 6 cm (P=0.02) influyeron positivamente sobre éste desenlace. Conclusión: Existe una influencia positiva sobre el pronóstico, de la tipificación en el cáncer de cérvix localmente avanzado tratado con quimioradiación basada en platino.

Caracterización de las células madre neoplásicas en el cáncer de endometrio

El carcinoma de endometrio (CE) es el tumor maligno más frecuente del tracto genital femenino en países desarrollados. Durante los últimos años, ha ganado firmeza la hipótesis de que el origen de los tumores se encuentra en la transformación de células indiferenciadas multipotenciales denominadas células madre somáticas (CMS) en células madre neoplásicas (CSC). Estudios recientes han observado la existencia de células madre en endometrios murinos y humanos; el presente proyecto pretende identificar, aislar, cultivar y caracterizar las CSC endometriales y estudiar los mecanismos moleculares responsables de su transformación. Nuestros resultados muestran que diferentes lineas celulares de cancer de endometrio expresan factores de célula indiferenciada. Un trabajo más extenso con la línea celular Ishikawa muestra la capacidad de estas células para crecer como esferas, diferenciarse a otros linajes y resistir al tratamiento radioterapéutico. Los resultados obtenidos nos permiten pensar que la línea Ishikawa es un buen modelo para el estudio de las CSC endometriales, aunque se necesitaría ampliar el estudio para ser concluyente.

Hypoxia and vasculature in models of lung cancer: implications for targeted therapeutics

Estudi realitzat a partir d’una estada a la Stanford University School of Medicine. Division of Radiation Oncology, Estats Units, entre 2010 i 2012. Durant els dos anys de beca postdoctoral he estat treballant en dos projectes diferents. En primer lloc, i com a continuació d'estudis previs del grup, volíem estudiar la causa de les diferències en nivells d'hipòxia que havíem observat en models de càncer de pulmó. La nostra hipòtesi es basava en el fet que aquestes diferències es devien a la funcionalitat de la vasculatura. Vam utilitzar dos models preclínics: un en què els tumors es formaven espontàniament als pulmons i l'altre on nosaltres injectàvem les cèl•lules de manera subcutània. Vam utilitzar tècniques com la ressonància magnètica dinàmica amb agent de contrast (DCE-MRI) i l'assaig de perfusió amb el Hoeschst 33342 i ambdues van demostrar que la funcionalitat de la vasculatura dels tumors espontanis era molt més elevada comparada amb la dels tumors subcutanis. D'aquest estudi, en podem concloure que les diferències en els nivells d'hipòxia en els diferents models tumorals de càncer de pulmó podrien ser deguts a la variació en la formació i funcionalitat de la vasculatura. Per tant, la selecció de models preclínics és essencial, tant pels estudi d'hipòxia i angiogènesi, com per a teràpies adreçades a aquests fenòmens. L'altre projecte que he estat desenvolupant es basa en l'estudi de la radioteràpia i els seus possibles efectes a l’hora de potenciar l'autoregeneració del tumor a partir de les cèl•lules tumorals circulants (CTC). Aquest efecte s'ha descrit en alguns models tumorals preclínics. Per tal de dur a terme els nostres estudis, vam utilitzar una línia tumoral de càncer de mama de ratolí, marcada permanentment amb el gen de Photinus pyralis o sense marcar i vam fer estudis in vitro i in vivo. Ambdós estudis han demostrat que la radiació tumoral promou la invasió cel•lular i l'autoregeneració del tumor per CTC. Aquest descobriment s'ha de considerar dins d'un context de radioteràpia clínica per tal d'aconseguir el millor tractament en pacients amb nivells de CTC elevats.

Complicaciones de la radioterapia cervicofacial. Osteorradionecrosis.

El tratamiento de los tumores de la cavidad bucal incluye en la mayoría de los casos la combinación de cirugía y radioterapia. Dentro de las secuelas de la radioterapia de la región cervicofacial podemos distinguir efectos agudos como radiodermitis, mucositis e hiposialia,y efectos tardios como necrosis cutánea, mucosa y ósea.La necrosis ósea u osteorradionecrosis es la complicación más severa de la radioterapia cervicofacial, siendo la mandibula la zona de la cavidad bucal que presenta una mayor incidencia. En este artículo presentamos una revisión bibliográfica de los efectos secundarios de la irradiación en la región de cabeza y cuello, haciendo especial hincapié en la osteorradionecrosis, describiendo su fisiopatología, clínica,diagnóstico,tratamiento y medidas preventivas encaminadas a minimizar o evitar esta patología.

Dental implications in oral cancer patients

Objectives. A study is made of the dental implications of oral cancer, with a view to avoiding the complications that appear once oncological treatment is started. Patients and Methods. The study comprised a total of 22 patients diagnosed with oral cancer according to clinical and histological criteria in the Service of Maxillofacial Surgery (Dental Clinic of the University of Barcelona, Spain) during the period 1996-2005, and posteriorly treated in different hospital centers in Barcelona. Results. Of the 22 patients diagnosed with oral cancer in our Service, the present study finally analyzed the 12 subjects who reported for the dental controls. As regards the remaining 10 patients, 5 had died and 5 could not be located; these subjects were thus excluded from the analysis. All of the smokers had abandoned the habit. The most common tumor location was the lateral margin of the tongue. None of the patients visited the dentist regularly before the diagnosis of oral cancer. T1N0M0 was the most common tumor stage. Surgery was carried out in 50% of the cases, while 8.4% of the patients received radiotherapy and 41.6% underwent surgery with postoperative radiotherapy. In turn, 66.6% of the patients reported treatment sequelae such as dysgeusia, xerostomia or speech difficulties, and one patient suffered osteoradionecrosis. Forty-one percent of the patients did not undergo regular dental controls after cancer treatment. As regards oral and dental health, 16.6% presented caries, and 50% had active periodontal disease. Conclusions. Protocols are available for preventing the complications of oral cancer treatment, and thus for improving patient quality of life. However, important shortcomings in the application of such protocols on the part of the public health authorities make it difficult to reach these objectives

Dental implications in oral cancer patients

Objectives. A study is made of the dental implications of oral cancer, with a view to avoiding the complications that appear once oncological treatment is started. Patients and Methods. The study comprised a total of 22 patients diagnosed with oral cancer according to clinical and histological criteria in the Service of Maxillofacial Surgery (Dental Clinic of the University of Barcelona, Spain) during the period 1996-2005, and posteriorly treated in different hospital centers in Barcelona. Results. Of the 22 patients diagnosed with oral cancer in our Service, the present study finally analyzed the 12 subjects who reported for the dental controls. As regards the remaining 10 patients, 5 had died and 5 could not be located; these subjects were thus excluded from the analysis. All of the smokers had abandoned the habit. The most common tumor location was the lateral margin of the tongue. None of the patients visited the dentist regularly before the diagnosis of oral cancer. T1N0M0 was the most common tumor stage. Surgery was carried out in 50% of the cases, while 8.4% of the patients received radiotherapy and 41.6% underwent surgery with postoperative radiotherapy. In turn, 66.6% of the patients reported treatment sequelae such as dysgeusia, xerostomia or speech difficulties, and one patient suffered osteoradionecrosis. Forty-one percent of the patients did not undergo regular dental controls after cancer treatment. As regards oral and dental health, 16.6% presented caries, and 50% had active periodontal disease. Conclusions. Protocols are available for preventing the complications of oral cancer treatment, and thus for improving patient quality of life. However, important shortcomings in the application of such protocols on the part of the public health authorities make it difficult to reach these objectives

EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe

Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th20th March 2013) and were invited to lecture on the subjects during the meeting (13th15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

β-catenin signalling in Glioblastoma multiforme and Glioma-initiating cells

Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with a poor prognosis. GBM can develop both “de novo” or evolve from a previous astrocytoma and is characterized by high proliferation and infiltration into the surrounding tissue. Following treatment (surgery, radiotherapy, and chemotherapy), tumors often reappear. Glioma-initiating cells (GICs) have been identified in GBM and are thought to be responsible for tumors initiation, their continued growth, and recurrence. β-catenin, a component of the cell-cell adhesion complex and of the canonical Wnt pathway, regulates proliferation, adhesion, and migration in different cell types. β-catenin and components of the Wnt canonical pathway are commonly overexpressed in GBM. Here, we review previous work on the role of Wnt/β-catenin signalling in glioma initiation, proliferation, and invasion. Understanding the molecular mechanisms regulating GIC biology and glioma progression may help in identifying novel therapeutic targets for GBM treatment.