Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas

'Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations (AU)

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

Safety in radiation oncology: transposition of directive 2013/59/EURATOM in the Spanish Radiation Oncology Departments-recommendations for its adequate and effective application.

INTRODUCTION: The Official Journal of the European Union published on January 17, 2014 the Council Directive 2013/59/EURATOM of December 5, 2013, which establishes basic safety standards for the protection against the dangers derived from the exposure to ionizing radiation, and should have been transposed to the regulations of the member countries of the European Union. METHODS: We carried out and exhaustive review of the Directive, to highlight its aspects referred to radiotherapy, in order to issue recommendations for its adequate and effective application in Spain. RECOMMENDATIONS FOR ITS TRANSPOSITION: A series of recommendations are issued, from highest to lowest organizational level: Legislative, Scientific Societies, Healthcare Centers, Radiation Oncology Departments, Radiation Oncologists and Patients. CONCLUSIONS: The implementation of what the transposition of the Directive to our legal order implies, besides the implication of the professionals, Centers and Administration, a need and a consumption of resources. If not enough are allocated, there is a risk that the innovation and improvement that the transposition would imply in order to raise the level of patient safety and the quality of Radiation Oncology in Spain will remain a paper tiger and, as the Romans said, "Non progredi est regredi", that is, when it does not go forward, it goes backwards.

Patient safety in radiation oncology in Spain: a need to change.

PURPOSE: The Working Group on Patient Safety and Quality of the Spanish Society of Radiation Oncology, revised the most relevant national and international recommendations, selecting a series of important aspects for patient safety, evaluating whether they are included in Spanish legislation MATERIALS AND METHODS: We have considered a concept as relevant to the patient safety in radiotherapy if so defined in at least 8 of the 16 documents reviewed. RESULTS: 12 subjects were selected: training and qualification, human resources, protocols, safety culture, communication, peer review, accreditation: audits, checklists, areas without interruptions, maps of processes and risks, prospective risk analysis, notification, registration and incident learning, and quality control of the equipment. CONCLUSIONS: At the legislative level, as well as the professional organizations and the health center directorates, the implementation of safety culture must continue to be fostered. Only in this environment will the tools and measures to increase patient safety be effective. The current Spanish legislation must be revised and updated, in accordance with directive 2013/59/EURATOM and the Patient Safety Strategy 2015-2020 of the Spanish National Health System, introducing the obligation to perform risk analysis and incidents management. Audits and accreditations must be carried out, thus raising the general level of practice of the specialty. In this process, the Spanish Society of Radiation Oncology must continue playing its fundamental role, collaborating with the institutions and the rest of the scientific societies involved in the radiotherapy process, issuing recommendations on patient safety and disseminating the safety culture in our specialty.

Time for radioimmunotherapy: an overview to bring improvements in clinical practice.

Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy. Within the last years, several antibodies blocking critical "checkpoints" that control the activation of T cells, the immune cells able to kill cancer cells, have been approved for the use in patients with different tumours. Unfortunately, these cases remain a minority. Over the last years, radiotherapy has been reported as a means to turn a patient's own tumour into an in situ vaccine and generate anti-tumour T cells in patients who lack sufficient anti-tumour immunity. Indeed, review data show that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumour responses and improve the outcome of metastatic solid tumours. Here, we review the principal tumours where research in this field has led to new knowledge and where radioimmunotherapy becomes a reality.

Quality indicators in radiation oncology: proposal of the Spanish Society of Radiation Oncology (SEOR) for a continuous improvement of the quality of care in oncology.

PURPOSE: Current cancer treatment options include surgical intervention, radiotherapy, and chemotherapy. The quality of the provision of each of them and their effective coordination determines the results in terms of benefit/risk. Regarding the radiation oncology treatments, there are not stabilised quality indicators to be used to perform control and continuous improvement processes for healthcare services. Therefore, the Spanish Society of Radiation Oncology has undertaken a comprehensive project to establish quality indicators for use with the information systems available in most Spanish healthcare services. METHODS: A two-round Delphi study examines consensus of several possible quality indicators (n = 28) in daily practice. These indicators were defined after a bibliographic search and the assessment by radiation oncology specialists (n = 8). They included aspects regarding treatment equipment, patient preparation, treatment, and follow-up processes and were divided in structure, process, and outcome indicators. RESULTS: After the evaluation of the defined quality indicators (n = 28) by an expert panel (38 radiation oncologist), 26 indicators achieved consensus in terms of agreement with the statement. Two quality indicators did not achieve consensus. CONCLUSIONS: There is a high degree of consensus in Spanish Radiation Oncology specialists on which indicators in routine clinical practice can best measure quality. These indicators can be used to classify services based on several parameters (patients, equipments, complexity of the techniques used, and scientific research). Furthermore, these indicators allow assess our current situation and set improvements' objectives.

Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) vs choline-positron emission tomography-computed tomography (choline-PET/CT) for selecting treatments in recurrent prostate cancer

Objective. To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. Materials and methods. This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. Results. Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. Conclusions. Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are complementary techniques. Future studies with more enrolled patients and a longer follow-up period will be required to confirm these data. The initial data show that the best technique for evaluating response after SBRT is choline-PET/CT (AU)

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Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) vs choline-positron emission tomography-computed tomography (choline-PET/CT) for selecting treatments in recurrent prostate cancer.

OBJECTIVE: To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. MATERIALS AND METHODS: This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. RESULTS: Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. CONCLUSIONS: Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are complementary techniques. Future studies with more enrolled patients and a longer follow-up period will be required to confirm these data. The initial data show that the best technique for evaluating response after SBRT is choline-PET/CT. Trial registration number NCT02858128.

Dolor irruptivo oncológico inducido por radioterapia: ¿es posible optimizar su tratamiento? / Radiotherapy-induced breakthrough cancer pain: is it possible to optimize its treatment?

Introducción: en el contexto de la radioterapia, el control del dolor irruptivo oncológico (DIO) supone un reto especial. El DIO ha sido definido por la Sociedad Española del Dolor (SED), la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Cuidados Paliativos (SECPAL) como una exacerbación del dolor súbita y transitoria, de gran intensidad (EVA > 7) y de corta duración (inferior a 20-30 minutos), que aparece sobre la base de un dolor persistente estable cuando este se encuentra reducido a un nivel tolerable (EVA < 5) mediante el uso de opioides mayores. Objetivos: el objetivo principal de este estudio fue evaluar la intensidad del DIO inducido por tratamientos oncológicos que incluyeran radioterapia (RT), tanto exclusiva como asociada a quimioterapia (RT/QT). Secundariamente, se evaluó la eficacia del tratamiento con fentanilo sublingual pautado para el control del DIO. Material y métodos: estudio observacional retrospectivo realizado en 110 pacientes reclutados en 19 Servicios de Radioterapia españoles. Los pacientes debían presentar DIO inducido por RT o RT/QT, con o sin medicación pautada y cuya intensidad fuera de una EVA > 6 en las últimas 24-48 h. Se establecieron controles en el momento basal, y a los 3, 7, 15 y 30 días. Resultados: se apreció un descenso en la media de los valores en la escala EVA según avanzó el estudio (EVA = 6 en el control 0 a EVA = 3 en el control 3), y las diferencias fueron significativas (p < 0,0001). La satisfacción con el tratamiento fue calificada como buena o excelente por el 85,3% de los pacientes y por el 92,7% de los investigadores. Conclusiones: los resultados de este estudio demuestran la eficacia del tratamiento del DIO con fentanilo sublingual en el contexto del tratamiento oncológico radioterápico, con un descenso significativo en los valores EVA frente al valor basal. La elevada satisfacción de los médicos y pacientes con este tratamiento refleja la eficacia y la comodidad del fentanilo sublingual en el control del DIO (AU)

Introduction: In the context of radiotherapy, control of breakthrough cancer pain (BTPc) is particularly challenging. BTPc has been defined by the Spanish Society of Pain (SED), the Spanish Society of Medical Oncology (SEOM) and the Spanish Society for Palliative Care (SECPAL) as a sudden and transient exacerbation of pain of great intensity (VAS > 7) and short (less than 20-30 minutes), which appears on the basis of a stable persistent pain when it is reduced to a tolerable level (VAS < 5) by using major opioids. Objectives: The main objective of this study was to assess the intensity of BTPc induced by cancer treatments that included radiotherapy (RT), both exclusive and associated with chemotherapy (RT/CT). Secondly, the efficacy of treatment was evaluated with fentanyl sublingual scheduled for BTPc control. Material and methods: Retrospective, observational study in 110 patients recruited in 19 Spanish Radiotherapy Services. Patients must have BTPc induced by RT or RT/CT, with or without medication prescribed and with an intensity outside a VAS > 6 in the last 24-48 h. Controls were established at baseline and at 3, 7, 15 and 30 days. Results: There was a decrease in mean values on the VAS scale as the study progressed (VAS = 6 in the control 0 to VAS = 3 in the control 3) and the differences were significant (p < 0.0001). Treatment satisfaction was rated as good or excellent by 85.3% of patients and 92.7% of researches. Conclusions: The results of this study demonstrate the efficacy of BTPc treatment with sublingual fentanyl in the context of the radiotherapy cancer treatment, with a significant decrease in VAS from baseline values . The high satisfaction among physicians and patients with this treatment reflects the efficacy and convenience of sublingual fentanyl in controlling BTPc (AU)

The contribution of the cone beam Kv (CBKvCT) to the reduction in toxicity of prostate cancer treatment with external 3D radiotherapy

OBJECTIVE: Show that verification through cone beam Kv CT (CBKvCT) in a series of patients treated with 3D external radiotherapy (3DRT) for prostate cancer (PC) is related to a reduction in acute and late toxicity levels. MATERIALS AND METHOD: A retrospective, non-randomized study of two homogeneous groups of patients treated between 2005 and 2008, 46 were verified using electronic portal devices (EPIDs) and 48 through CBKvCT. They received 3DRT for localized PC (T1-T3N0M0) and were prescribed the same doses. Treatment was simulated and planned with the same criteria with the same equipment with a median follow-up time of 24 months (12-54 months). Urinary and gastrointestinal toxicity was determined using Common Toxicity Criteria scale, version 4 and RTOG scales. Statistical analysis of data was performed where p < 0.005 being significative. RESULTS AND DISCUSSION: With an overall median follow-up time of 24 months, the levels of proctitis were, respectively, 19.56, 15.21 and 15.2 % in the first group, compared with 4.17, 2.08 and 8.33 % in the second. Statistically, less total and late proctitis, late rectal bleeding, anal fissure, total and acute haematuria, total and acute urinary frequency and total urinary incontinence was observed. No statistically significant evidence of a lowering in toxicity neither in terms of acute and late dysuria nor of a relationship to the TNM, Gleason or PSA or in the grade of stability. CONCLUSION: Verification through CBKvCT in this series is associated with a statistically significant lowering toxicity. This justifies its use. Greater monitoring would be necessary to assess the impact of verification at the level of biochemical control (AU)

Uncertainties and CTV to PTV margins quantitative assessment using cone-beam CT technique in clinical application for prostate, and head and neck irradiation tumours.

PURPOSE To evaluate the magnitude of systematic and random errors from a subset of 100 prostate and 26 head and neck (H&N) cancer patients treated with conventional conformal radiotherapy and using image-guided radiotherapy (IGRT). After treatment, the uncertainties involved and the CTV to PTV margin were evaluated. MATERIAL AND METHODS An Elekta Synergy® linear accelerator was used, taking advantage of 3D on-board computed tomography. IGRT with no-action level (NAL) protocol was applied, reporting the 3D translation and rotation corrections. A statistical study was performed to analyse systematic, random and interobserver uncertainties, and, finally, to obtain the CTV to PTV margins. RESULTS The H&N patients' uncertainties found were smaller than those of prostate patients. The CTV to PTV margins assessed, following the guidelines found in the literature, in the three dimensions of space (right-left, superior-inferior, anterior-posterior) were (5.3, 3.5, 3.2) mm for H&N and (7.3, 7.0, 9.0) mm for prostate cancer treatments. CONCLUSIONS It was found that assessing all the involved uncertainties within radiation treatments was very revealing; their quality improves using IGRT techniques and performing extensive data analysis.

Uncertainties and CTV to PTV margins quantitative assessment using cone-beam CT technique in clinical application for prostate, and head and neck irradiation tumours

PURPOSE To evaluate the magnitude of systematic and random errors from a subset of 100 prostate and 26 head and neck (H&N) cancer patients treated with conventional conformal radiotherapy and using image-guided radiotherapy (IGRT). After treatment, the uncertainties involved and the CTV to PTV margin were evaluated. MATERIAL AND METHODS An Elekta Synergy® linear accelerator was used, taking advantage of 3D on-board computed tomography. IGRT with no-action level (NAL) protocol was applied, reporting the 3D translation and rotation corrections. A statistical study was performed to analyse systematic, random and interobserver uncertainties, and, finally, to obtain the CTV to PTV margins. RESULTS The H&N patients' uncertainties found were smaller than those of prostate patients. The CTV to PTV margins assessed, following the guidelines found in the literature, in the three dimensions of space (right-left, superior-inferior, anterior-posterior) were (5.3, 3.5, 3.2) mm for H&N and (7.3, 7.0, 9.0) mm for prostate cancer treatments. CONCLUSIONS It was found that assessing all the involved uncertainties within radiation treatments was very revealing; their quality improves using IGRT techniques and performing extensive data analysis (AU)

Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo- and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia (AU)

Theoretical aspects of implementation of kilovoltage cone-beam CT onboard linear accelerator for image-guided radiotherapy

The main objective of image-guided radiation therapy (IGRT) equipment is to reduce and correct inherent errors in external radiotherapy processes. At the present time, there are different IGRT systems available, but here we will refer exclusively to the kilovoltage cone-beam CT onboard linear accelerator (CBkVCT) and the different aspects that, from a clinical point of view, should be taken into consideration before the implementation of this equipment (AU)

Retroperitoneal tumour radiotherapy: clinical improvements using kilovoltage cone beam computed tomography

We present a clinical case of a patient diagnosed with a retroperitoneal sarcoma, which received preoperative treatment with daily verification via computed tomography obtained with kilovoltage cone beam. We compare the benefit of this treatment compared to other conventional treatment without image guiding, reporting quantitative results (AU)

Tratamiento multidisciplinario actual del cáncer de próstata metastásico / Current multiapproach treatment of metastatic prostate cancer

El cáncer de próstata es una causa común de muerte en hombres occidentales. La morbimortalidad asociada suele ser consecuencia directa de la diseminación ósea, presente en hasta un 50 por ciento de los pacientes en el momento del diagnóstico. El objetivo del tratamiento de estos enfermos metastásicos es la prevención o paliación de los síntomas y de las complicaciones. El arsenal terapéutico es amplio e incluye hormonoterapia, radioterapia externa, radiofármacos, cirugía, quimioterapia, bisfosfonatos y nuevos fármacos (inhibidores de la angiogénesis, inmunoterapia y fármacos que actúan sobre la diferenciación celular). En la elección del tratamiento se deben considerar múltiples factores: la condición de andrógeno-dependiente o andrógeno-independiente, ya que la terapia hormonal constituye el primer escalón del tratamiento; la localización y extensión de la destrucción ósea; la gravedad del cuadro; la disponibilidad de las diferentes terapias; el estado del paciente; el pronóstico de supervivencia y la relación coste-efecto. Las indicaciones de algunas de estas terapias están claramente establecidas mientras que otras están todavía en estudio para determinar su eficacia, la pauta de tratamiento y las indicaciones. En este artículo se realiza una revisión y actualización de dichos tratamientos (AU)

[Current multidisciplinary treatment of metastatic prostatic cancer]. / Tratamiento multidisciplinario actual del cáncer de próstata metastásico.

Prostate cancer is one of the commonest causes of cancer-related death in the western world. The morbi-mortality associated is usually a direct consequence of metastatic spread to bone, in up to 50% of patients at first presentation. The aim of treatment of metastatic patients is to alleviate and to prevent the distressing symptoms. The approach include hormone-therapy, radiotherapy, radio-nuclides, surgery, chemotherapy, bisphosphonates and new drugs (agents that inhibit angiogenesis, immunotherapy and therapies that affect the differentiation). Decisions about therapy must also take into consideration the androgen-dependent or independent, so hormone-therapy is the first step of the treatment; the number and location of bone metastases; the severity of symptoms; the available of therapies; the status performance of patient; the prognosis and the cost-effect relationship. Some treatments have established indications whereas others are still in process of study in order to determinate their efficacy, their model of treatment and their indications. This article revises and updates these treatments.