RESUMEN
PURPOSE: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA.
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Adenocarcinoma , Neoplasias Pulmonares , Neoplasias Pancreáticas , Radiocirugia , Humanos , Radiocirugia/métodos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Variaciones Dependientes del Observador , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirugía , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias PancreáticasRESUMEN
BACKGROUND: This prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year. METHODS: Eligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1-6, 8-13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals. RESULTS: Between 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48-66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59-100], 53% [34-83], 41% [23-73], and 29% [14-61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40-88], 35% [19-67], and 29% [14-61], corresponding cumulative incidences of loco-regional progressions were 18% [4-39%], 35% [14-58%], and 41% [17-64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%). CONCLUSIONS: Dose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound. Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE ) and authorized to proceed on 2006-09-25.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Anciano , Quimioradioterapia/efectos adversos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosificación RadioterapéuticaAsunto(s)
Neoplasias Hepáticas/cirugía , Alemania , Hepatectomía , Humanos , Instrumentos QuirúrgicosRESUMEN
INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used in metastasized patients receiving targeted/immunotherapy. Information on safety and effectivity of concurrent SBRT and targeted/immunotherapy remains limited, resulting in a lack of consensus on treatment strategies. This study aimed to investigate how SBRT-experienced centers in German-speaking countries combine both therapies. MATERIALS AND METHODS: Patterns-of-care of combined treatment with SBRT and targeted/immunotherapy were assessed in 27 radiation oncology centers (19 German, 1 Austrian and 7 Swiss centers). A survey was performed to analyze the details of SBRT, SBRT planning and combined modality treatment. Consensus was defined as ≥75% agreement among participants. RESULTS: Most participants (60%) were university centers. SBRT for oligometastases has been performed since the year 2008â¯(median, range 1997-2016), since then a median of 140 cases (5-1100) of SBRT have been performed. In all, 67% performed concurrent SBRT and targeted agents. BRAF inhibitors and VEGF/EGFR inhibitors (bevacizumab [90%], erlotinib [11%], sorafenib [19%], lapatinib [4%]) were considered a contraindication. Bevacizumab was never given simultaneously with SBRT; other agents were given concurrently in 7-52% of centers. A majority (59%) paused targeted agents 1 week before/after SBRT. Only 1 center reduced SBRT dose when combined with targeted agents. CONCLUSION: Although evidence for safety and efficacy of concurrent SBRT and targeted agents is limited, it is regularly performed outside of clinical trials. The survey showed consensus not to combine SBRT with antiangiogenic agents, especially bevacizumab. Furthermore, SBRT with concurrent BRAF inhibitors should be practiced with caution and BRAF inhibitors should be paused at least 1 week before SBRT.
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Comparación Transcultural , Terapia Molecular Dirigida/métodos , Metástasis de la Neoplasia/radioterapia , Pautas de la Práctica en Medicina , Radiocirugia/métodos , Radioterapia/métodos , Centros Médicos Académicos , Terapia Combinada , Contraindicaciones , Alemania , Humanos , Inmunoterapia , Encuestas y Cuestionarios , SuizaRESUMEN
BACKGROUND: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. METHODS: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. RESULTS: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. CONCLUSION: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Tomografía Computarizada por Rayos X/métodos , Carga Tumoral , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Stereotactic body radiotherapy (SBRT) in pancreatic cancer can be limited by its proximity to organs at risk (OAR). In this analysis, we evaluated the toxicity and efficacy of two different treatment approaches in patients with locally recurrent or oligometastatic pancreatic cancer. MATERIALS AND METHODS: According to the prescription method, patients were divided in two cohorts (C1 and C2). The planning target volume (PTV) was created through a 4 mm expansion of the internal target volume. In C2, a subvolume was additionally created, a simultaneous integrated protection (SIP), which is the overlap of the PTV with the planning risk volume of an OAR to which we prescribed a reduced dose. RESULTS: In all, 18 patients were treated (7 with local recurrences, 9 for oligometastases, 2 for both). Twelve of 23 lesions were treated without SIP (C1) and 11 with SIP (C2). The median follow-up was 12.8 months. Median overall survival (OS) was 13.2 (95% confidence interval [CI] 9.8-14.6) months. The OS rates at 6 and 12 months were 87 and 58%, respectively. Freedom from local progression for combined cohorts at 6 and 12 months was 93 and 67% (95% CI 15-36), respectively. Local control was not statistically different between the two groups. One patient in C2 experienced grade ≥3 acute toxicities and 1 patient in C1 experienced a grade ≥3 late toxicity. CONCLUSION: The SIP approach is a useful prescription method for abdominal SBRT with a favorable toxicity profile which does not compromise local control and overall survival despite dose sacrifices in small subvolumes.
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Adenocarcinoma/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias Pancreáticas/radioterapia , Protección Radiológica/métodos , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/métodos , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Estudios de Cohortes , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Órganos en Riesgo/efectos de la radiación , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Análisis de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
The aim of this study was to retrospectively analyze the long-term effectiveness of combined chemoradiation as the definitive treatment of locally advanced cancers of the cervical esophagus. Patients received high-dose external beam radiotherapy and concurrent cisplatin-based chemotherapy. Some patients received intraluminal brachytherapy as a boost. In addition, a majority of the patients received cisplatin-based induction chemotherapy before definitive chemoradiation. Fifty-five patients (46 men, 9 women, median age 58 years, range 35-72 years) with cancers of the cervical esophagus (stage II: 20; stage III: 35 patients) were treated with definitive chemoradiation (median dose 60 Gy, range 50-70 Gy). Actuarial overall survival rates at 2, 3, 5, and 10 years were 35%, 29%, 25%, and 10%, respectively. Thirteen long-term survivors were observed with a follow-up of more than 5 years. Neither gender nor age, tumor length, tumor grade, or clinically detectable lymph node metastases was significant prognostic factors for survival. Twenty-four patients (44%) developed local or regional recurrences, 15 (27%) distant metastases, and 8 (15%) patients developed a second malignancy. Acute and late toxicity of this treatment schedule was moderate. Concurrent chemoradiation offers a chance of long-term survival for locally advanced unresectable carcinomas of the cervical esophagus, with long-term survival rates above 24% and acceptable toxicity. These results substantiate the use of chemoradiation as a curative treatment option for cervical esophageal cancer.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Esófago/patología , Adenocarcinoma/patología , Adulto , Anciano , Braquiterapia , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Etopósido/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Quimioterapia de Inducción/métodos , Leucovorina/administración & dosificación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Cuello , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Photocatalytic reduction of mercury in aqueous solutions using PW12O40(3-) or SiW12O40(4-) as photocatalysts has been studied as a function of irradiation time, concentration of Hg(II), polyoxometalate, and organic substrate in the presence or absence of dioxygen. The photocatalytic cycle starts with irradiation of polyoxometalate, goes through the oxidation of, for instance, propan-2-ol (used as sacrificial reagent), and closes with the reoxidation of reduced polyoxometalate by Hg2+ ions. Mercury(II) is reduced to mercury(I) and finally to Hg(0) giving a dark-gray deposit, following a staged one-by-one electron process and a first-order kinetics in [Hg2+]. The process is slightly more efficient in the absence of dioxygen, while the increase of either catalyst or propan-2-ol concentration results in the augmentation of the rate of reduction till a certain point where it reaches a plateau. The results show that this method is suitable for a great range of mercury concentration from 20 to 800 ppm achieving almost complete recovery of mercury up to nondetected traces (<50 ppb). In addition, this homogeneous process demonstrates advantages such as the lack of necessity for separation of the zero state metal from the catalyst and ensures that the precipitation of metal will not poison the catalyst or hinder its photocatalytic activity.
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Mercurio/metabolismo , Fotoquímica , Compuestos de Tungsteno/química , Contaminantes Químicos del Agua/metabolismo , Catálisis , Cinética , Mercurio/toxicidad , Compuestos Orgánicos/metabolismo , Oxidación-Reducción/efectos de la radiación , Oxígeno/química , Espectrofotometría Ultravioleta , Contaminantes Químicos del Agua/toxicidadRESUMEN
Cyclosporine (CsA) (37.4 mumol/kg per day for 7 days) treated female Wistar rats exhibited significantly decreased creatinine clearance (Ccr) and body weight loss (BWL), but had neither proteinuria (PU) nor alteration in their urine volume (V). Light microscopic (LM) sections of rat kidneys showed that all kidneys were affected by lesions, mainly diffuse vacuolization. These changes were associated with decreased urinary excretion ratios of 6-ketoprostaglandin F1 alpha to thromboxane B2 (6kPGF1 alpha/TXB2) and prostaglandin E2 to TXB2 (PGE2/TXB2). When OKY-046, a TXA2-synthetase inhibitor or nifedipine (NFD), a calcium channel blocker and an antagonist of endotheline (ET), were administered in addition to CsA, they restored Ccr and increased urine V but they did not prevent BWL. LM sections showed that only 5 or 7 out of 9 kidneys of animals were affected, respectively. These changes were associated with prevention of the diminished ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 mainly in the OKY-046 treated animals. In conclusion, our results suggest that inhibitors of TXA2 or antagonists and/or inhibitors of endothelin play a protective role in the development of the dysfunction induced by CsA. However, the protection observed using OKY-046 and NFD did not reach that obtained by evening primrose oil (EPO) or Ketanserine (KTS), substances which prevented the fall of Ccr and BWL. Furthermore, with these protective agents only 5 out of 9 kidneys were affected and the lesions were of minor importance.
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Bloqueadores de los Canales de Calcio/uso terapéutico , Ciclosporina/toxicidad , Inhibidores Enzimáticos/uso terapéutico , Inmunosupresores/toxicidad , Metacrilatos/uso terapéutico , Nifedipino/uso terapéutico , Insuficiencia Renal/prevención & control , Animales , Creatinina/farmacocinética , Interacciones Farmacológicas , Eicosanoides/orina , Ácidos Grasos Esenciales/uso terapéutico , Femenino , Ketanserina/uso terapéutico , Pruebas de Función Renal , Túbulos Renales/patología , Ácidos Linoleicos , Tasa de Depuración Metabólica , Oenothera biennis , Aceites de Plantas , Ratas , Ratas Wistar , Ácido gammalinolénicoRESUMEN
Acute renal failure (ARF) induced with large doses of Gentamicin (GM) (an aminoglycoside) was associated with increased urinary TXB (TXA) excretion which provoked a decrease of the ratios of urinary PGE2/TXB2 and 6-keto-PGF1 alpha (PGI2)/TXB2 excretions. Furthermore, as indicated by light microscopy most of the epithelial cells lining the proximal tubules show obvious lesions varying from swelling of their cytoplasm to complete necrosis. Either the inhibitor, OKY-O46, of TXA-synthetase, or volume expansion (VE) with isotonic saline (IS) of the experimental animals diminished urinary TXB excretion which provoked 1) augmentation of the ratios of urinary PGE/TXB and 6-keto-PGF1 alpha/TXB excretions, 2) elevation of creatinine clearance (Ccr) and 3) diminution of proteinuria (PU). This protection against ARF-by OKY-O46 and VE can a can be seen in microscopic sections where necrosis of proximal tubules is almost absent. Only a few proximal tubules show swelling of their epithelial cells and some focal areas of tubule necrosis. We suggest that the metabolites of arachidonic acid (AA), TXA2 a (potent vasoconstrictor agent) and prostaglandins (PGE2 and PGI2), (potent vasodilator factors), play an important role in the development (TXA2) or in the prevention (PGs) of ARF induced by this antibiotic.
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Lesión Renal Aguda/inducido químicamente , Gentamicinas/toxicidad , Tromboxano A2/biosíntesis , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Arginina Vasopresina/metabolismo , Catecolaminas/metabolismo , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Metacrilatos/farmacología , Prostaglandinas/metabolismo , Ratas , Ratas Endogámicas , Sistema Renina-Angiotensina/efectos de los fármacos , Tromboxano-A Sintasa/antagonistas & inhibidoresAsunto(s)
Lesión Renal Aguda/prevención & control , Ácidos Grasos Esenciales/farmacología , 6-Cetoprostaglandina F1 alfa/orina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/fisiopatología , Animales , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Hipolipemiantes/farmacología , Ácidos Linoleicos , Cloruro de Mercurio/toxicidad , Oenothera biennis , Aceites de Plantas , Prostaglandinas E/orina , Ratas , Ratas Endogámicas BN , Tromboxano B2/orina , Ácido gammalinolénicoAsunto(s)
Acrilatos/uso terapéutico , Ácidos Grasos Esenciales/uso terapéutico , Glomerulonefritis por IGA/tratamiento farmacológico , Metacrilatos/uso terapéutico , Tromboxano-A Sintasa/antagonistas & inhibidores , Animales , Femenino , Glomerulonefritis por IGA/inducido químicamente , Glomerulonefritis por IGA/orina , Ácidos Linoleicos , Cloruro de Mercurio , Oenothera biennis , Aceites de Plantas , Prostaglandinas/orina , Proteinuria , Ratas , Ratas Endogámicas BN , Ácido gammalinolénicoRESUMEN
The excretion rates of renal thromboxane B2 (TXB2) and 6-ketoPGF1 alpha, the stable chemical metabolites of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) respectively, PGE2 and sodium were determined in normal and saline-loaded rats treated with the thromboxane synthetase inhibitor imidazole. In normal rats the administration of imidazole in doses which did not affect renal 6-keto-PGF1 alpha and PGE2 excretion but selectively inhibited renal TXB2 excretion, significantly increased the sodium excretion rate. Volume expansion with saline increased renal PGE2 and 6-ketoPGF1 alpha excretion but did not alter renal TXB2 excretion. The increase in renal prostaglandin excretion was accompanied by an increased sodium excretion rate. The administration of imidazole to saline-loaded animals also decreased renal TXB2 excretion but did not alter the increased excretion of renal PGE2 and 6-ketoPGF1 alpha. This reduction in renal thromboxane biosynthesis by imidazole further increased the sodium excretion rate. We suggest that TXA2 is a potent antinatriuretic factor as well as the most potent vasoconstrictor agent known.