Carmen González San Segundo

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial

BACKGROUND The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. METHODS In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. FINDINGS Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. INTERPRETATION Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. FUNDING Spanish National Health Investigation Fund, AstraZeneca.

An Innovative Tool for Intraoperative Electron Beam Radiotherapy Simulation and Planning: Description and Initial Evaluation by Radiation Oncologists

PURPOSE Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. METHODS AND MATERIALS The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose--volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. RESULTS High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 ± 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). CONCLUSIONS The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input.

Retrasos e interrupciones: la dificultad para irradiar en el tiempo ideal

ResumenAdministrar la dosis prescrita en el tiempo programado, sin retrasos en el inicio ni interrupciones en su ejecución, es un objetivo fundamental en los tratamientos conradioterapia (RT). En algunas localizaciones tumorales, se ha objetivado su influencia pronóstica en el control local y en la evolución de los pacientes.El presente estudio analiza las causas de los retrasos en el inicio de la RT así como, una vez iniciado el tratamiento, los principales motivos que prolongan la irradiación. En la revisión de la literatura realizada, los cánceres de cabeza y cuello, cérvix, mama y pulmón, parecen ser los más “perjudicados” por las interrupciones o demoras en la administración de la dosis total programada.En el caso del retraso en el inicio, se mencionan como las principales causas de demora: las listas de espera, la falta de recursos y la complejidad de los tratamientos actuales de RT. El inicio tan precoz como sea posible, en los tratamientos radicales y paliativos, y el intervalo de 6–8 semanas, en los tratamientos complementarios, son las recomendaciones recogidas en la mayoría de los estudios.Las interrupciones durante el tratamiento incluyen las paradas técnicas previstas para el mantenimiento programado de las unidades, que suponen el 60%, así como las producidas por toxicidad y averías. La influencia de las mismas, según el momento y la localización tumoral, así como los mecanismos para compensar la prolongación del tiempo total de tratamiento, completan la revisión bibliográfica llevada a cabo en este trabajo.AbstractPrescribed total radiation dose should be administered within in a specific time-frame and delays in commencing treatment and/or unplanned interruptions in radiation delivery are unacceptable because, in certain cancer sites, treatment-time prolongation can have a deleterious effect on local tumour control, and on patient outcomes.The present review evaluated the causes of initial treatment delays as well as interruptions in the scheduled radiotherapy. The literature search high-lighted a significant concern in avoiding treatment-time prolongation in head and neck, cervix, breast and lung cancer.Among the causes involved in delay in radiotherapy commencement factors such as waiting lists, lack of material and human resources, and an increase complexity in planning, simulation and verification are highlighted. Most authors recommend radiotherapy commencement as soon as possible in radical (exclusive irradiation with active tumour present) and palliative situations with a maximum delay of no more than 6 to 8 weeks in the case of adjuvant radiotherapy (post-resection) programs.Interruptions during the course of treatment include: planned unit maintenance and servicing, acute patient toxicity or unexpected malfunction of linear accelerators; this last feature has the most deleterious effect on patients as well as radiotherapy practitioners. Interruptions that impact on the programmed time-course for radiotherapy needs to be compensated-for so as assure the biological equivalence in treatment efficacy with respect to cancer site and stage.Prescribed total radiation dose should be administered within in a specific time-frame and delays in commencing treatment and/or unplanned interruptions in radiation delivery are unacceptable because, in certain cancer sites, treatment-time prolongation can have a deleterious effect on local tumour control, and on patient outcomes. The present review evaluated the causes of initial treatment delays as well as interruptions in the scheduled radiotherapy. The literature search highlighted a significant concern in avoiding treatment-time prolongation in head and neck, cervix, breast and lung cancer. Among the causes involved in delay in radiotherapy commencement factors such as waiting lists, lack of material and human resources, and an increase complexity in planning, simulation and verification are highlighted. Most authors recommend radiotherapy commencement as soon as possible in radical (exclusive irradiation with active tumour present) and palliative situations with a maximum delay of no more than 6 to 8 weeks in the case of adjuvant radiotherapy (post-resection) programs. Interruptions during the course of treatment include: planned unit maintenance and servicing, acute patient toxicity or unexpected malfunction of linear accelerators; this last feature has the most deleterious effect on patients as well as radiotherapy practitioners. Interruptions that impact on the programmed time-course for radiotherapy needs to be compensated-for so as assure the biological equivalence in treatment efficacy with respect to cancer site and stage.

Informed consent in radiation oncology: is consenting easier than informing?

The patient’s right to be informed has been universally recognized and reflected in the legal system of many countries. This right to correct and complete information on behalf of the patient and his admission to proceed with the recommended diagnostic or therapeutic procedure is formalized in the document commonly known as informed consent. Although the legal and bioethical considerations regarding this document have been exhaustively discussed and consensuated, its content continues to create certain doubts and uncertainties. The formal content and the manner in which the consent is obtained are the most difficult aspects.In this article, we analyze what should be included in the written informed consent, with regard to the totality of the information which the patient receives, who should inform, and how the consent should be obtained, as well as how to reflect the different aspects of the variety of radiotherapeutic procedures in the informed consent.

Does Radiotherapy Have to Justify its Use in Hodgkin's Disease?

In 1902, Pusey performed and published the ® rst treatment with radiotherapy (RT) in a patient with Hodgkin’s disease (HD). Later, Gilbert, in 1931, formulated the need of a systematic plan of irradiation on all affected nodal regions while insisting on the need to achieve remission of all the lesions with the ® rst treatment used. Beginning in the 1950s, Kaplan and the Stanford group, in the megavolt era, de® ned the modern techniques of RT and established the principles of RT planning in HD that are still applicable today (1). In 1994, Lee stated that RT, applied on its own, was still the best treatment for HD in the initial stages (2). More than 50 study series with follow-ups of more than 20 years support this statement (3 ± 8). Nevertheless, in routine practice as well as in the development of protocols and clinical trials, an almost unanimous abandonment of RT as the single treatment in HD is emerging. Combined treatment (CT) is becoming standard practice without, as Gustafsson (9, 10) and Ng & Mauch (11) have recently stated, bibliographic support demonstrating signi® cant improvements in overall survival. The reasons for RT losing ground in initial-stage treatment have been debated and:or, justi® ed on the basis of:

Corrigendum to "Uroncor consensus statement: Management of biochemical recurrence after radical radiotherapy for prostate cancer: From biochemical failure to castration resistance". [Rep. Pract. Oncol. Radiother. 20 (2015) 259-272].

[This corrects the article DOI: 10.1016/j.rpor.2015.04.003.].

Radioterapia tras prostatectomía radical: factores descriptivos, evolutivos y de pronóstico en una práctica asistencial emergente

Resumen es: Objetivo: Recientemente se han comunicado firmes evidencias por la EORTC (European Organisation for Research and Treatment of Cancer - ensayo 22911) y el...

Radioterapia preoperatoria en el melanoma de coroides con afectación extraescleral

ResumenEl melanoma de coroides con afectación extraescleral representa aproximadamente el 4%–10% de los melanomas uveales. Constituye un reconocido factor pronóstico adverso, tanto para la recurrencia local como para la supervivencia global. La enu-cleación asociada a la resección quirúrgica de la extensión extraescleral es el tratamiento de elección, aunque los pobres resultados obtenidos con el tratamiento quirúrgico aislado han animado a la búsqueda de tratamientos complementarios a la cirugía. Se presenta la experiencia del Hospital Universitario de Valladolid en el tratamiento de 6 casos de melanoma con afectación extraescleral tratados con radioterapia preenucleación, analizando los resultados obtenidos, los cambios radioinducidos y la similitud con los casos publicados en la literatura.AbstractExtrascleral extension is present in 4%–10% of uveal melanomas. Its a relevant risk factor for local recur-rence and survival. Enucleation with surgical resection of the extrascleral extension is the treatment of choice. The poor results obtained with isolated surgery, have encouraged to search adjunctive treatments. We present the experience of the University Hospital of Valladolid in the treatment of 6 cases of uveal melanoma with extrascleral extension treated with pre-enucleation radiotherapy. We analize the results, the histopathologic findings induced in the enucleated eyes and the cases published in the literature.