Delta radiomics analysis of Magnetic Resonance guided radiotherapy imaging data can enable treatment response prediction in pancreatic cancer.

BACKGROUND: Magnetic Resonance Image guided Stereotactic body radiotherapy (MRgRT) is an emerging technology that is increasingly used in treatment of visceral cancers, such as pancreatic adenocarcinoma (PDAC). Given the variable response rates and short progression times of PDAC, there is an unmet clinical need for a method to assess early RT response that may allow better prescription personalization. We hypothesize that quantitative image feature analysis (radiomics) of the longitudinal MR scans acquired before and during MRgRT may be used to extract information related to early treatment response. METHODS: Histogram and texture radiomic features (n = 73) were extracted from the Gross Tumor Volume (GTV) in 0.35T MRgRT scans of 26 locally advanced and borderline resectable PDAC patients treated with 50 Gy RT in 5 fractions. Feature ratios between first (F1) and last (F5) fraction scan were correlated with progression free survival (PFS). Feature stability was assessed through region of interest (ROI) perturbation. RESULTS: Linear normalization of image intensity to median kidney value showed improved reproducibility of feature quantification. Histogram skewness change during treatment showed significant association with PFS (p = 0.005, HR = 2.75), offering a potential predictive biomarker of RT response. Stability analyses revealed a wide distribution of feature sensitivities to ROI delineation and was able to identify features that were robust to variability in contouring. CONCLUSIONS: This study presents a proof-of-concept for the use of quantitative image analysis in MRgRT for treatment response prediction and providing an analysis pipeline that can be utilized in future MRgRT radiomic studies.

Dose-mass inverse optimization for minimally moving thoracic lesions.

In the past decade, several different radiotherapy treatment plan evaluation and optimization schemes have been proposed as viable approaches, aiming for dose escalation or an increase of healthy tissue sparing. In particular, it has been argued that dose-mass plan evaluation and treatment plan optimization might be viable alternatives to the standard of care, which is realized through dose-volume evaluation and optimization. The purpose of this investigation is to apply dose-mass optimization to a cohort of lung cancer patients and compare the achievable healthy tissue sparing to that one achievable through dose-volume optimization. Fourteen non-small cell lung cancer (NSCLC) patient plans were studied retrospectively. The range of tumor motion was less than 0.5 cm and motion management in the treatment planning process was not considered. For each case, dose-volume (DV)-based and dose-mass (DM)-based optimization was performed. Nine-field step-and-shoot IMRT was used, with all of the optimization parameters kept the same between DV and DM optimizations. Commonly used dosimetric indices (DIs) such as dose to 1% the spinal cord volume, dose to 50% of the esophageal volume, and doses to 20 and 30% of healthy lung volumes were used for cross-comparison. Similarly, mass-based indices (MIs), such as doses to 20 and 30% of healthy lung masses, 1% of spinal cord mass, and 33% of heart mass, were also tallied. Statistical equivalence tests were performed to quantify the findings for the entire patient cohort. Both DV and DM plans for each case were normalized such that 95% of the planning target volume received the prescribed dose. DM optimization resulted in more organs at risk (OAR) sparing than DV optimization. The average sparing of cord, heart, and esophagus was 23, 4, and 6%, respectively. For the majority of the DIs, DM optimization resulted in lower lung doses. On average, the doses to 20 and 30% of healthy lung were lower by approximately 3 and 4%, whereas lung volumes receiving 2000 and 3000 cGy were lower by 3 and 2%, respectively. The behavior of MIs was very similar. The statistical analyses of the results again indicated better healthy anatomical structure sparing with DM optimization. The presented findings indicate that dose-mass-based optimization results in statistically significant OAR sparing as compared to dose-volume-based optimization for NSCLC. However, the sparing is case-dependent and it is not observed for all tallied dosimetric endpoints.

SU-E-T-479: Skin Dose from Flattening Filter Free Beams: A Monte Carlo Investigation.

PURPOSE: Flattening filter free (FFF) beams in radiotherapy have advantages such as shorter treatment delivery time and lower out-of-field dose compared with conventional flattened beams. This study investigates in detail the skin dose induced by FFF beams from a TrueBeam accelerator (Varian Medical Systems, Palo Alto, CA) using Monte Carlo method. METHODS: Phase space files generated using real geometry of a TrueBeam accelerator above the jaws, were used as the input radiation source files in beam simulation for various field sizes using BEAMnrc. Phase space files for various field sizes were generated at the phantom surface. DOSXYZnrc was used for dose calculations in phantom and in patient using the generated phase space files as source input files. RESULTS: The calculated percentage depth dose curves and profiles in water agreed with measurements within ± 2% for the high dose region and ±2 mm in the penumbra. The peak fluence of a 6 MV FFF beam with the same electron beam incident on the target is about 3 times that of a flattened beam . The mean energy of a 6 MV FFF beam is 0.92-0.95 MeV while it is 1.18-1.30 MeV for the flattened beam. Due to the mean energy difference, the dose in a 6 MV FFF beam is about 6% (of the maximum dose, or 12% of local dose) higher at depth of 1 mm compared with a flattened beam. CONCLUSIONS: Due to the lower mean photon energy, in an FFF beam the surface (skin) dose is slightly higher compared to the conventional flattened beam of the same field size.

SU-E-T-553: Dose-Mass Vs. Dose-Volume Optimization: A Phantom Study.

PURPOSE: To demonstrate the merits of mass-based optimization in comparison with volume-based optimization using a simple test phantom. METHODS: Dose-volume-histogram-based (DVH-based) quadratic objective functions are converted into dose-mass-histogram-based (DMH-based) objective functions by multiplying per-voxel volumes by per-voxel densities within the objective. A digital phantom with a 1.0 g/cm3 target is constructed for irradiation with two beams: one beam path contains a 0.2 g/cm3 volume-of-interest (VOI0.2) while the orthogonal beam-path contains an equal-volume 0.8 g/cm3 VOI (VOI0.8). Monitor-units are computed to achieve a 100 cGy average target dose for each individual beam, and for two-beam DVH-based and DMH-based optimizations. RESULTS: For single-beam irradiation through VOI0.2, the average dose to VOI0.2 is 20.5 cGy. For single-beam irradiation through VOI0.8, the average dose to VOI0.8 is 25.2 cGy. Traversing the low density volume results in ∼23% lower dose. When DVH- and DMH-based optimizations are performed such that target dose-volume-histograms of the optimizations match, for the DVH optimization 60% vs. 40% of the dose is delivered through VOI0.2 vs. VOI0.8. For DMH-optimization, the split between dose delivered through VOI0.2 vs. VOI0.8 is 70% vs. 30%. CONCLUSIONS: When density is constant, there is no difference between DVH- and DMH-based optimizations. However, in heterogeneous media, DMH and DVH solutions differ when low and high density materials have the same dose objectives. Delivering target dose through lower density VOIs facilitates target dose deposition due to a decrease in attenuating material, and the decreased attenuation lowers dose to the low density VOI. From mathematical and physical points of view dose-mass optimization is more general than dose-volume optimization.

SU-E-J-167: Optimal Number of Respiratory Phases in 4D PET for Radiotherapy Planning: Motion-Simulated Phantom Study.

PURPOSE: Four-dimensional PET/CT is increasingly used in radiotherapy treatment planning. One issue that is still under investigation is the optimal number of bins or phases into which the respiratory cycle needs to be divided. We performed 4D PET moving phantom study and compared results between 6 and 10 bins. METHODS: A Jaszczak Phantom™ containing six hollow spheres (0.95 - 3.18 cm inner diameters) was used. Three sinusoidal motion patterns were accomplished with peak-to-peak amplitudes of 1, 1.5 and 2.0 cm with a respiratory period of 5 s. The background and the six spheres were filled with 18F-FDG solution to achieve three SBR: 1:3.65, 1:7.95, and 1:10.22. Data were collected in 3-D mode for 10 min. Images were reconstructed using OSEM reconstruction: 32 subsets with 2 iterations, variable FWHM Gaussian post-filter 5-8 mm, and using image matrix sizes of 128×128, 192×192 and 256×256. The spheres were auto-segmented using pre-calculated optimal thresholds for a 1:1 volumetric correlation between actual- and PET-delineated spheres from static phantom studies. RESULTS: According to the static data the following set of parameters are optimal for static PET target (sphere) delineation: OSEM reconstruction with 32 subsets and 2 iterations, FWHM of 5 mm, and image size 256×256. The 4D data studies (with pre-calculated optimal thresholds) have shown that a 6-bin set shows less volume distortions then the 10-bin set. CONCLUSIONS: The authors found that 6-bin reconstruction is more reliable for delineation of a target in motion than 10-bin reconstruction. Further investigation with optimal thresholds obtained from 4D data, not static, is required no conflict of interest for all authors.

SU-E-J-187: Evaluation of the Effects of Dose on 4DCT-Calculated Lung Ventilation.

PURPOSE: To investigate the effects of radiation therapy (RT) treatment dose on ventilation. METHODS: Optical flow deformable image registration of the normal end-expiration and end-inspiration phases of 4DCT images was used to correlate the voxels between the two phases. 4DCT sets from before and after RT were used to derive ventilation for 3 SBRT lung patients. Planning dose and normalized ventilation were superimposed on the CT volume resulting in each voxel having a volume, a normalized ventilation and a dose. From these values a 3D dose-ventilation-volume surfaces was created. The surface was integrated over dose to reduce the 3D surface to a 2D histogram that is easier to interpret. RESULTS: For lung tissue regions receiving more than 20 Gy, a decrease in ventilation was observed in the three patients. Patient A (time between scans, T=26 months) showed an increase in ventilation for regions receiving a dose smaller than 20 Gy, whereas patients B (T=3 months) and C (T=6 months) did not show any change for these regions. Mean ventilation within the 20 Gy region for patient A was 0.57 before RT and 0.51 after RT; and 0.54 before and 0.48 after RT for the 30 Gy region. Mean ventilation for the 20 Gy region for patient B was 0.49 before RT and 0.47 after RT, for the 30 Gy region mean ventilation was 0.49 Gy before and 0.45 Gy after RT. Patient C's mean ventilation for the 20 Gy region was 0.54 before RT and 0.50 after RT, for the 30 Gy region mean ventilation was 0.54 before RT and 0.49 after RT. CONCLUSIONS: Ventilation before and after radiation therapy can be measured using 4DCT and deformable image registration techniques. In a preliminary application of this approach for three patients, changes in ventilation were observed with a weak correlation between ventilation change and dose. Partially supported by a grant from Varian Medical Systems.

Clinical feasibility of TBI with helical tomotherapy.

Our purpose was to present the clinical feasibility of TBI with helical tomotherapy (HT) in four patients with AML. Treatment planning, delivery, dose verification and summation, toxicity and patient outcomes for each patient are presented. TBI prescription was set in such a manner that 80% of the clinical target volume received 12 Gy in six fractions, at two fractions per day. Dose reconstruction was carried out by recontouring the regions of interest in the daily pretreatment megavoltage computed tomography of each individual fraction and calculating its corresponding dose. A deformable registration model was used for dose summation of all individual fractions. Differences between planned and delivered doses were calculated. Average planned and delivered doses to the regions of interest differed by up to 2.7%. TBI toxicity was limited to radiotherapy oncology group grade 1 dermatitis in all patients and grade 1 headache in one patient. Two patients are alive with no evidence of disease and no GVHD. Two patients died of GVHD, but there was no evidence of disease at the time of death. We conclude that HT simplifies the process of TBI. Dose verification is possible with HT showing small differences between plan and delivered doses.

Diferencias en las presiones del canal anal y la sensibilidad rectal en pacientes con incontinencia anal, estreñimiento crónico y sujetos sanos / No disponible

Introducción: Existe gran variabilidad en los hallazgos manométricos entre pacientes con incontinencia anal (IA) y sujetos sanos. La correlación entre las presiones del canal anal y la IA no es exacta por el amplio rango de valores normales. Objetivos: Estudio prospectivo para evaluar diferencias en las presiones del canal anal y en la sensibilidad rectal en pacientes con IA, estreñimiento crónico (EC) y sujetos sanos. Material y métodos: Noventa y cuatro pacientes con IA, 36 pacientes con EC y 15 sujetos sanos. Se obtuvieron: edad, sexo, presión de reposo, longitud del canal anal (LCA), presión de máxima contracción voluntaria (PMCV), duración de la contracción voluntaria, primera sensación, sensación de urgencia y máximo volumen tolerado (MVT). Estudio estadístico: test de Kruskal-Wallis, test de Mann-Whitney, regresión logística multinomial. Resultados: Se encontraron diferencias significativas en la edad (p < 0,001), la presión de reposo (p < 0,001), la LCA (p < 0,001) y la PMCV (p < 0,01) en el grupo de IA con respecto a los otros dos grupos. El volumen para la primera sensación fue significativamente más bajo en los sujetos sanos que en los otros dos grupos (p < 0,05). El volumen de urgencia y el MVT fueron menores en el grupo con IA con respecto a los otros dos grupos (p < 0,001). En el análisis multivariante la edad, la presión de reposo y el volumen de la primera sensación y de la urgencia aumentan el riesgo relativo de IA. Conclusiones: La mayor edad, la disminución presión basal del canal anal y la alteración del umbral sensorial rectal aumentan el riesgo de IA(AU)

Introduction: There exist a great variability in the manometric findings between patients with anal incontinence (AI) and healthy subjects. The correlation between the pressures of the anal canal and the AI is not exact by the wide rank of normal values. Objectives: Prospective study to evaluate differences in the pressures of the anal canal and in rectal sensitivity in patients with AI, chronic constipation (CC) and healthy subjects. Material and methods: Ninety four patients with AI, 36 patients with CC and 15 healthy subjects were included. The following data were obtained: age, sex, resting pressure, anal canal length (ACL), squeeze maximum pressure (SMP), squeeze pressure duration (SPD), first sensation, urge and maximum tolerated volume (MTV). Statistical study: test of Kruskal-Wallis, test of Mann-Whitney, and multinomial logistic regression test. Results: There were significant differences in the resting pressure (p < 0.001), the ACL (p < 0.001) and the SMP (p < 0.01) in the group of AI with respect to the other two groups. The volume for the first sensation was significantly lower in the healthy subjects than that in the other two groups (p < 0.05). The urge volume and the MVT were smaller in the group with AI with respect to the other groups (p < 0.001). In multivariate analysis the age, the resting pressure and the volume for the first sensation and urge increase the relative risk for AI. Conclusions: The greater age, the decrease in anal canal resting pressure and the alteration of rectal sensation increase the risk for AI(AU)

Differences in the pressures of canal anal and rectal sensitivity in patients with fecal incontinence, chronic constipation and healthy subjects.

INTRODUCTION: There exists a great variability in the manometric findings between patients with anal incontinence (AI) and healthy subjects. The correlation between the pressures of the anal canal and the AI is not exact by the wide rank of normal values. OBJECTIVES: Prospective study to evaluate differences in the pressures of the anal canal and in rectal sensitivity in patients with AI, chronic constipation (CC) and healthy subjects. MATERIAL AND METHODS: Ninety four patients with AI, 36 patients with CC and 15 healthy subjects were included. The following data were obtained: age, sex, resting pressure, anal canal length (ACL), squeeze maximum pressure (SMP), squeeze pressure duration (SPD), first sensation, urge and maximum tolerated volume (MTV). Statistical study: test of Kruskal-Wallis, test of Mann-Whitney, and multinomial logistic regression test. RESULTS: There were significant differences in the resting pressure (p < 0.001), the ACL (p < 0.001) and the SMP (p < 0.01) in the group of AI with respect to the other two groups. The volume for the first sensation was significantly lower in the healthy subjects than that in the other two groups (p < 0.05). The urge volume and the MVT were smaller in the group with AI with respect to the other groups (p < 0.001). In multivariate analysis the age, the resting pressure and the volume for the first sensation and urge increase the relative risk for AI. CONCLUSIONS: The greater age, the decrease in anal canal resting pressure and the alteration of rectal sensation increase the risk for AI.

Altered calcium dynamics mediates P19-derived neuron-like cell responses to millimeter-wave radiation.

Intracellular calcium oscillations have long been recognized as a principal mediator of many vital cellular activities. Furthermore, Ca(2+) dynamics can be modulated by external physical cues, including electromagnetic fields. While cellular responses to low-frequency electric fields have been established, the possible non-thermal effects of millimeter-wave (MMW) radiation are still a subject of discussion and debate. We used mouse embryonic stem cell-derived neuronal cells and a custom-built 94 GHz applicator to examine in real time the altered Ca(2+) oscillations associated with MMW stimulation. MMW irradiation at 18.6 kW/m(2) nominal power density significantly increased the Ca(2+) spiking frequency in the cells exhibiting Ca(2+) activity. The N-type calcium channels, phospholipase C enzyme, and actin cytoskeleton appear to be involved in mediating increased Ca(2+) spiking. Reorganization of the actin microfilaments by a 94 GHz field seems to play a crucial role in modulating not only Ca(2+) activity but also cell biomechanics. Many but not all observed cellular responses to MMW were similar to thermally induced effects. For example, cell exposure to a 94 GHz field induced nitric oxide production in some morphologically distinct neuronal cells that could not be reproduced by thermal heating of the cells up to 42 degrees C. The highest observed average temperature rise in the MMW exposure chamber was approximately 8 degrees C above the room temperature, with possible complex non-uniform microscopic distribution of heating rates at the cell level. Our findings may be useful to establish quantitative molecular benchmarks for elucidation of nociception mechanisms and evaluation of potential adverse bioeffects associated with MMW exposure. Moreover, control of Ca(2+) dynamics by MMW stimulation may offer new tools for regulation of Ca(2+)-dependent cellular and molecular activities, for example, in tissue engineering applications.

PET imaging of heat-inducible suicide gene expression in mice bearing head and neck squamous cell carcinoma xenografts.

The ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancer gene therapy to be successful. One approach to address this is through the use of promoters that can be controlled by external means, such as hyperthermia. In this regard, we constructed a replication-deficient adenovirus that consists of a mutated herpes simplex virus 1 thymidine kinase (mTK) fused to enhanced green fluorescent protein (EGFP) under the control of the full-length human heat shock (HS) 70b promoter. The virus (AdHSmTK-EGFP) was evaluated both in vitro and in vivo in oral squamous cell carcinoma SCC-9 cells for expression of both mTK and EGFP. The in vitro expression of mTK-EGFP was validated using both (3)H-penciclovir and fluorescence-activated cell sorting assays. These studies show that specific expression could be achieved by heating the cells at 41 degrees C for 1 h, whereas little expression was observed using high doses of virus without hyperthermia. The vector was also evaluated in vivo by direct intratumoral injection into mice bearing SCC-9 xenografts. These studies demonstrated tumor expression of mTK-EGFP after ultrasound heating of the tumors by radioactive biodistribution assays, histology and microPET imaging. These in vivo results, which demonstrate HS-inducible transgene expression using PET imaging, provide a means for noninvasive monitoring of heat-induced gene therapy in local tumors, such as oral squamous cell carcinomas.

Modeling of carbon fiber couch attenuation properties with a commercial treatment planning system.

The purpose of this work is to evaluate the modeling of carbon fiber couch attenuation properties with a commercial treatment planning system (TPS, Pinnacle3, v8.0d). A carbon fiber couch (Brain-Lab) was incorporated into the TPS by automatic contouring of all transverse CT slices. The couch shape and dimensions were set according to the vendor specifications. The couch composition was realized by assigning appropriate densities to the delineated contours. The couch modeling by the TPS was validated by absolute dosimetric measurements. A phantom consisting of several solid water slabs was CT scanned, the CT data set was imported into the TPS, and the carbon fiber couch was auto-contoured. Open (unblocked) field plans for different gantry angles and field sizes were generated. The doses to a point at 3 cm depth, placed at the linac isocenter, were computed. The phantom was irradiated according to the dose calculation setup and doses were measured with an ion chamber. In addition, percent depth dose (PDD) curves were computed as well as measured with radiographic film. The calculated and measured doses, transmissions, and PDDs were cross-compared. Doses for several posterior fields (0 degree, 30 degrees, 50 degrees, 75 degrees, 83 degrees) were calculated for 6 and 18 MV photon beams. For model validation a nominal field size of 10 x 10 cm2 was chosen and 100 MU were delivered for each portal. The largest difference between computed and measured doses for those posterior fields was within 1.7%. A comparison between computed and measured transmissions for the aforementioned fields was performed and the results were found to agree within 1.1%. The differences between computed and measured doses for different field sizes, ranging from 5 x 5 cm2 to 25 x 25 cm2 in 5 cm increments, were within 2%. Measured and computed PDD curves with and without the couch agree from the surface up to 30 cm depth. The PDDs indicate a surface dose increase resulting from the carbon fiber couch field modification. The carbon fiber couch attenuation for individual posterior oblique fields (75 degrees) can be in excess of 8% depending on the beam energy and field size. When the couch is contoured in Pinnacle3 its attenuation properties are modeled to within 1.7% with respect to measurements. These results demonstrate that appropriate contouring together with relevant density information for the contours is sufficient for adequate modeling of carbon fiber supporting devices by modern commercial treatment planning systems.