Quantification of the uncertainties of a biological model and their impact on variable RBE proton treatment plan optimization.

PURPOSE: In proton radiation therapy, a relative biological effectiveness (RBE) equal to 1.1 is currently assumed, although biological experiments show that it is not constant. The purpose of this study was to quantify the uncertainties of a published biological model and explore their impact on variable RBE treatment plan (TP) optimization. METHODS: Two patient cases with a high and a low (α/ß)x tumor were investigated. Firstly, intensity modulated proton therapy TPs assuming constant RBE were derived, and subsequently the variable RBE weighted dose (RWD), including the uncertainty originating in the fit to the experimental data and the uncertainty of the (α/ß)x, were calculated. Secondly, TPs optimized for uniform biological effect assuming a variable RBE were created using the worst case tissue specific (α/ß)x. RESULTS: For the nasopharyngeal cancer patient, the uncertainty of (α/ß)x corresponded to a CTV D98 confidence interval (CI) of (-2, +4)% while for the fit parameter CI was (-2,+1)%. For the standard fractionation prostate case the (α/ß)x CI was (-7,+5)% and the fit parameter CI was (-3,+3)%. For the hypofractionated case both CIs were (-1,+1)%. In both patient cases, the RBE in most organs at risk (OARs) was significantly underestimated by the constant RBE approximation, whereas the situation was not as definite in the target volumes. Overdosage of OARs was reduced by using the biological effect optimization. CONCLUSION: For the two patient cases, the RWD uncertainty from the fit parameter in the biological model contributed non-negligibly to the total uncertainty, depending on the patient case and the organ. The presented optimization strategy is a basic method for robust biological effect optimization to reduce potential consequences caused by the (α/ß)x uncertainty.

Variance-based sensitivity analysis of biological uncertainties in carbon ion therapy.

PURPOSE: Biological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2) are needed for treatment planning and plan evaluation in carbon ion therapy. We present a model-independent, Monte Carlo based sensitivity analysis (SA) approach to quantify the impact of different uncertainties on the biological models. METHODS AND MATERIALS: The Monte Carlo based SA is used for the evaluation of variations in biological parameters. The key property of this SA is the high number of simulation runs, each with randomized input parameters, allowing for a statistical variance-based ranking of the input variations. The potential of this SA is shown in a simplified one-dimensional treatment plan optimization. Physical properties of carbon ion beams (e.g. fragmentation) are simulated using the Monte Carlo code FLUKA. To estimate biological effects of ion beams compared to X-rays, we use the Local Effect Model (LEM) in the framework of the linear-quadratic (LQ) model. Currently, only uncertainties in the output of the biological models are taken into account. RESULTS/CONCLUSIONS: The presented SA is suitable for evaluation of the impact of variations in biological parameters. Major advantages are the possibility to access and display the sensitivity of the evaluated quantity on several parameter variations at the same time. Main challenges for later use in three-dimensional treatment plan evaluation are computational time and memory usage. The presented SA can be performed with any analytical or numerical function and hence be applied to any biological model used in carbon ion therapy.

SU-E-T-610: Impact of Variable Beam Spot Size on Treatment Time in Particle Therapy.

PURPOSE: The dosimetric advantage of particle therapy comes with a much higher infrastructure investment and operation costs. Increasing patient throughput is a key factor to manage operation costs. We investigate the impact of variable beam spot sizes on treatment time and discuss the tradeoffs involved. METHODS: The following realistic assumptions were used. (1) The beam traveling speed is independent of the beam spot size. (2) The beam spot is a 2D Gaussian. Changing the beam spot size implies varying the standard deviation. (3) The maximum beam intensity is a constant independent of the beam spot size. Increasing the beam spot reduces the fluence. (4) Varying the beam spot size incurs in a reset time penalty.A 2D tumor was used in the study. Dose calculations were based on pencil beam kernels from GEANT4.The total treatment time is divided into the beam travel time, the beam-on time, andthe time for changing the spot size. RESULTS: We found that: (1) Changing the beam spot size has no impact on the beam-on time, because the maximum beam intensity is independentof the beam spot and increasing the beam spot only reduces the fluence. (2) Larger beam spot size shortens the total travel time inversely proportional to the radius of the beam spot. (3) Plans with different beam spot sizes have similar dosimetric qualities. (4) If higher beam intensity could be used for larger beam spot size, savings in beam-on time would be inversely proportional to the intensity available. CONCLUSIONS: We have studied the interplay among beam intensity, travel time, and beam size reset time for a scanning beam with variable beam spot size. Our initial studies show necessary conditions for and limitations on savings in total treatment times. Further studies are being carried out to find additional time saving sources. Supported in part by NSF CBET-0853157.

Patología del confluente biliopancreático / Pathology of the bili-pancreatic confluent

El presente trabajo tiene el proposito de contribuir al conocimiento de la fisiopatologia del confluente biliopancreático, mediante procedimientos clínicos, paraclinicos, radiologicos, histológicos y anatomopatologicos. Para lograrlo se estudiaron desde el doble punto de vista radiológico e histologico, 33 piezas de autopsia de otros tantos pacientes fallecidos por causas distintas de la patologia biliar y pancreatica; y de 40 pacientes con patologia blliopancreatica, sometidos a estudios clinicos y paraclinicos previos al tratamiento quirurgico que consistio en esfinterotomia transduodenal y esfinteroplastia, siendo esta ultima el procedimiento de eleccion en pacientes con colecistocoledocolitiasis, colelitiasis asociada a dilatacion del coledoco o con pancreatitis. En tales casos los resultados clinicos fueron positivos. Con criteria de estudio histopatologico, se tomo biopsia de la papila de Vater en un grupo de los pacientes en quienes se practicó esfinterotomia transduodenal.

[Behçet's disease with an onset prior to the appearance of chronic myeloid leukemia]. / Enfermedad de Behçet de inicio previo a la aparición de leucemia mieloide crónica.

The case of a Ph-positive female patient with chronic myeloid leukemia (CML) is reported. The patient presented a cutaneous-mucous picture prior to the appearance of the hemopathy consisting of genitals ulcers, buccal aphthae and nodular cutaneous lesions the study of which demonstrated panniculitis. The lesions improved with the administration of low doses of prednisone and colchicine. The CML evolved to a blastic crisis of a monocytic phenotype at 14 months of diagnosis leading to death of the patient. The cutaneous-mucous picture was catalogued as Becçet disease (BD) according to the criteria of the International Study Group for Behçet Disease. Given the lack of serologic tests or pathognomonic histologic lesions the difficulty in the diagnosis of BD is commented upon and the differential diagnosis of this disease, particularly with respect to the Sweet syndrome, is discussed.

[Granulomatous peritonitis due to starch. Apropos of a case]. / Peritonitis granulomatosa por almidón. A propósito de un caso.

The authors present a case of granulomatous peritonitis due to starch in a 47-year-old female. This is an infrequent, but clinically important, process. Contamination occurs mainly through rubber gloves. The symptomatology is varied and simulates a picture of acute abdomen. The diagnosis rests on examination of the liquid obtained by peritoneocentesis or peritoneal biopsy. The histopathologic picture is that of a granulomatous reaction to foreign matter, with giant cells that exhibit birefringent granules in the form of the Maltese cross. Medical management is based on the use of steroids and anti-inflammatory agents.