Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival.

AIMS: The definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. MATERIALS AND METHODS: This monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan-Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. RESULTS: Between 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4-93.4), 74.9% (95% confidence interval 66.1-81.7) and 57.2% (95% confidence interval 45.8-67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06-3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01-3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34-4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4-70.9), 31.5% (95% confidence interval 22.8-40.6) and 24.7% (95% confidence interval 16.0-34.3). CONCLUSIONS: This study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Risk-group Classification by Recursive Partitioning Analysis of Patients Affected by Oligometastatic Renal Cancer Treated with Stereotactic Radiotherapy.

AIMS: Due to the absence of consensus on metastases-directed treatment in kidney cancer, we conducted an analysis of patients treated with stereotactic radiotherapy (SRT) on cranial or extracranial metastases to classify them in survival class risk according to pre-treatment characteristics. MATERIALS AND METHODS: We included oligometastatic kidney cancer patients treated with SRT on up to five metastases. Concomitant systemic treatment was allowed. End points included overall survival and the binary classification tree approach with recursive partitioning analysis was applied to stratify patients into overall survival risk groups. RESULTS: In total, 129 patients were treated on 242 metastases. The brain was the most common site (34.71%), followed by lung (25.62%). With a median follow-up of 19.4 months, 1- and 3-year overall survival were 82.62 and 55.11%. The recursive partitioning analysis identified four prognostic classes. Class 1 included patients aged ≤ 65 years treated on extracranial metastases, with 3-year overall survival of 82.66%. Class 2 included patients aged > 65 years, without history of metastatic bone disease, treated on extracranial metastases, with a 3-year overall survival of 67.91%. Patients aged > 65 years and a history of bone disease, treated on extracranial metastases, were classified as class 3, with a 3-year overall survival of 37.50%. Class 4 included patients treated on brain metastases, with a 3-year overall survival of 9.70%. CONCLUSION: We produced a stratification model that can predict survival of oligometastatic kidney cancer patients treated with metastases-directed SRT. Site of disease, patient's age and presence of bone disease can help clinicians in the decision-making process.

The impact of scanning data measurements on the Acuros dose calculation algorithm configuration.

BACKGROUND: Many dose calculation algorithms for radiotherapy planning need to be configured for each clinical beam using pre-defined measurements. An optimization process adjusts the physical parameters able to estimate the energy released in the medium in any geometrical condition. This work investigates the impact of measured input data quality on the configuration of the type "c" Acuros-XB dose calculation algorithm in the Eclipse (Varian Medical Systems) treatment planning system. METHODS: Different datasets were acquired with the BeamScan water phantom (PTW) to configure 6 MV beams, for both flattened (6X) and flattening filter free mode (6FFF) for a Varian TrueBeam: (i) a correct dataset measured using a Semiflex-3D ion chamber, (ii) a set in missing lateral scatter conditions (MLS), (iii) a set with incorrect effective point of measurement (EPoM), (iv) sets acquired with PinPoint-3D chamber, DiodeP, microDiamond detectors. The Acuros-XB dose calculation algorithm (version 15.6) was configured using the reference dataset, the sets measured with the different detectors, with intentional errors, and using the representative beam data (RBD) made available by the vendor. The physical parameters obtained from each optimization process (spectrum, mean radial energy, electron contamination), were analyzed and compared. Calculated data were finally compared against the input and reference measurements. RESULTS: Concerning the physical parameters, the configurations presenting the largest differences were the MLS conditions (mean radial energy) and the incorrect EPoM (electron contamination). The calculation doses relative to the input data present low accuracy, with mean differences > 2% in some conditions. The PinPoint-3D ion chamber presented lower accuracy for the 6FFF beam. Regarding the RBD, calculations compared well with the input data used for the configuration, but not with the reference data. CONCLUSION: The MLS conditions and the incorrect setting of the EPoM lead to erroneous configurations and should be avoided. The choice of an appropriate detector is important. Whenever the representative beam data is used, a careful check under more clinical geometrical conditions is advised.

The Potential Role of Intensity-modulated Proton Therapy in the Regional Nodal Irradiation of Breast Cancer: A Treatment Planning Study.

AIMS: To investigate the role of intensity-modulated proton therapy (IMPT) for regional nodal irradiation in patients with breast carcinoma in comparison with volumetric-modulated arc therapy (VMAT). MATERIALS AND METHODS: A cohort of 20 patients (10 in the breast-conserving surgery group and 10 post-mastectomy patients with tissue expander implants) was investigated. Proton plans were also computed using robust optimisation methods. Plan quality was assessed by means of dose-volume histograms and scored with conventional metrics. Estimates of the risk of secondary cancer induction (excess absolute risk, EAR) were carried out, taking into account fractionation, repopulation and repair. RESULTS: Concerning target coverage, the data proved a substantial equivalence of VMAT and IMPT: for example, coverage for the 50 Gy target, expressed in terms of V98%, was 47.8 ± 0.4, 47.6 ± 0.4, 47.3 ± 0.8, consistent with the objective of 47.5 Gy, for post-mastectomy patients for the three groups of patients. Also, the conformality of the dose distributions was similar for the two techniques, about 1.1, without statistically significant differences. Organ at risk planning aims were achieved for all structures for both techniques. The mean dose to the ipsilateral lung was 10.8 ± 1.1, 6.2 ± 0.8, 7.2 ± 1.0; for the contralateral lung was 3.2 ± 0.7, 0.3 ± 0.2, 0.4 ± 0.2; for the contralateral breast was: 3.1 ± 0.7, 0.3 ± 0.3 and 0.3 ± 0.3, whereas it was 3.9 ± 0.9, 0.4 ± 0.3 and 0.5 ± 0.5, respectively, for the heart for VMAT, IMPT and robust IMPT plans over the whole group of patients. Robust optimisation affected the near-to-maximum dose values for contralateral lung and breast, the mean dose for the heart and ipsilateral lung, with a deterioration ranging from 20 to 40% of the nominal value of IMPT plans (e.g. from 8.1 ± 6.4 to 11.4 ± 8.8 for the heart compared with 16.2 ± 5.2 for the VMAT plans). The numerical values of EAR per 10 000 patient-years were about one order of magnitude higher for VMAT than for IMPT for contralateral structures: 11.66 ± 2.01, 0.89 ± 0.80, 0.98 ± 0.77 for the contralateral breast and the three groups of plans, respectively; 14.31 ± 2.75, 1.42 ± 0.80, 1.78 ± 0.87 for the contralateral lung; and 34.86 ± 2.64, 18.85 ± 2.15, 20.98 ± 2.35 for the ipsilateral lung. CONCLUSION: IMPT with or without robust optimisation seems to be a potentially promising approach for the radiation treatment of breast cancer when nodal volumes should be irradiated. This was measured in terms of dosimetric advantage and predicted clinical benefit. In fact, the significant reduction in estimated EAR could add further clinical value to the dosimetric sparing of the organs at risk achievable with IMPT.

RapidPlan knowledge based planning: iterative learning process and model ability to steer planning strategies.

PURPOSE: To determine if the performance of a knowledge based RapidPlan (RP) planning model could be improved with an iterative learning process, i.e. if plans generated by an RP model could be used as new input to re-train the model and achieve better performance. METHODS: Clinical VMAT plans from 83 patients presenting with head and neck cancer were selected to train an RP model, CL-1. With this model, new plans on the same patients were generated, and subsequently used as input to train a novel model, CL-2. Both models were validated on a cohort of 20 patients and dosimetric results compared. Another set of 83 plans was realised on the same patients with different planning criteria, by using a simple template with no attempt to manually improve the plan quality. Those plans were employed to train another model, TP-1. The differences between the plans generated by CL-1 and TP-1 for the validation cohort of patients were compared with respect to the differences between the original plans used to build the two models. RESULTS: The CL-2 model presented an improvement relative to CL-1, with higher R2 values and better regression plots. The mean doses to parallel organs decreased with CL-2, while D1% to serial organs increased (but not significantly). The different models CL-1 and TP-1 were able to yield plans according to each original strategy. CONCLUSION: A refined RP model allowed the generation of plans with improved quality, mostly for parallel organs at risk and, possibly, also the intrinsic model quality.

Collimator scatter factor: Monte Carlo and in-air measurements approaches.

BACKGROUND: Linac output as a function of field sizes has a phantom and a head scatter component. This last term can be measured in-air with appropriate build-up ensuring a complete electron equilibrium and the absence of the contaminant electrons. Equilibrium conditions could be achieved using a build-up cap or a mini-phantom. Monte Carlo simulations in a virtual phantom mimicking a mini-phantom were analysed with the aim of better understanding the setup conditions for measuring the collimator scatter factor that is the head scatter component of the linac output factors. METHODS: Beams of 6 and 15 MV from a TrueBeam, with size from 4 × 4 to 40 × 40 cm2 were simulated in cylindrical acrylic phantoms 20 cm long, of different diameters, from 0.5 to 4 cm, with the cylinder axis coincident with the beam central axis. The PRIMO package, based on PENELOPE Monte Carlo code, was used. The phase-space files for a Varian TrueBeam linac, provided by the linac vendor, were used for the linac head simulation. Depth dose curves were analysed, and collimator scatter factors estimated at different depth in the different phantom conditions. Additionally, in-air measurements using acyrilic and brass build-up caps, as well as acrylic mini-phantom were acquired for 6 and 18 MV beams from a Varian Clinac DHX. RESULTS: The depth dose curves along the cylinders were compared, showing, in each phantom, very similar curves for all analysed field sizes, proving the correctness in estimating the collimator scatter factor in the mini-phantom, provided to position the detector to a sufficient depth to exclude electron contamination. The results were confirmed by the measurements, where the acrylic build-up cap showed to be inadequate to properly estimate the collimator scatter factors, while the mini-phantom and the brass caps gave reasonable measurements. CONCLUSION: A better understanding of the beam characteristics inside a virtual mini-phantom through the analysis of depth dose curves, showed the critical points of using the acrylic build-up cap, and suggested the use of the mini-phantom for the collimator scatter factor measurements in the medium-large field size range.

Evaluation of target dose inhomogeneity in breast cancer treatment due to tissue elemental differences.

BACKGROUND: Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues. METHODS: CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV_lob and CTV_fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed. RESULTS: From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions. CONCLUSION: Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.

Small field characterization of a Nanochamber prototype under flattening filter free photon beams.

INTRODUCTION: Nanochambers present some advantages in terms of energy independence and absolute dose measurement for small field dosimetry in the SBRT scenario. Characterization of a micro-chamber prototype was carried out both under flattened and flattening-filter-free (FFF) beams with particular focus on stem effect. METHODS: The study included characterization of leakage and stem effects, dose rate and dose per pulse dependence, measurement of profiles, and percentage depth doses (PDDs). Ion collection efficiency and polarity effects were measured and evaluated against field size and dose per pulse. The 6_MV, 6_MV_FFF and 10_MV FFF beams of a Varian EDGE were used. Output factors were measured for field sizes ranging from 0.8×0.8cm2 to 20×20cm2 and were compared with other detectors. RESULTS: The 2mm diameter of this chamber guarantees a high spatial resolution with low penumbra values. In orthogonal configuration a strong stem (and cable) effect was observed for small fields. Dose rate and dose per pulse dependence were <0.3% and 0.6% respectively for the whole range of considered values. The Nanochamber exhibits a field size (FS) dependence of the polarity correction >2%. The OF values were compared with other small field detectors showing a good agreement for field sizes >2×2cm2. The large field over-response was corrected applying kpol(FS). CONCLUSIONS: Nanochamber is an interesting option for small field measurements. The spherical shape of the active volume is an advantage in terms of reduced angular dependence. An interesting feature of the Nanochamber is its beam quality independence and, as a future development, the possibility to use it for small field absolute dosimetry.

RapidPlan head and neck model: the objectives and possible clinical benefit.

BACKGROUND: To evaluate a knowledge based planning model for RapidPlan (RP) generated for advanced head and neck cancer (HNC) patient treatments, as well its ability to possibly improve the clinical plan quality. The stability of the model was assessed also for a different beam geometry, different dose fractionation and different management of bilateral structures (parotids). METHODS: Dosimetric and geometric data from plans of 83 patients presenting HNC were selected for the model training. All the plans used volumetric modulated arc therapy (VMAT, RapidArc) to treat two targets at dose levels of 69.96 and 54.45 Gy in 33 fractions with simultaneous integrated boost. Two models were generated, the first separating the ipsi- and contra-lateral parotids, while the second associating the two parotids to a single structure for training. The optimization objectives were adjusted to the final model to better translate the institutional planning and dosimetric strategies and trade-offs. The models were validated on 20 HNC patients, comparing the RP generated plans and the clinical plans. RP generated plans were also compared between the clinical beam arrangement and a simpler geometry, as well as for a different fractionation scheme. RESULTS: RP improved significantly the clinical plan quality, with a reduction of 2 Gy, 5 Gy, and 10 Gy of the mean parotid, oral cavity and laryngeal doses, respectively. A simpler beam geometry was deteriorating the plan quality, but in a small amount, keeping a significant improvement relative to the clinical plan. The two models, with one or two parotid structures, showed very similar results. NTCP evaluations indicated the possibility of improving (NTCP decreasing of about 7%) the toxicity profile when using the RP solution. CONCLUSIONS: The HNC RP model showed improved plan quality and planning stability for beam geometry and fractionation. An adequate choice of the objectives in the model is necessary for the trade-offs strategies.

Organs at risk in lung SBRT.

Lung stereotactic body radiotherapy (SBRT) is an accurate and precise technique to treat lung tumors with high 'ablative' doses. Given the encouraging data in terms of local control and toxicity profile, SBRT has currently become a treatment option for both early stage lung cancer and lung oligometastatic disease in patients who are medically inoperable or refuse surgical resection. Dose-adapted fractionation schedules and ongoing prospective trials should provide further evidence of SBRT safety trying to reduce toxicities and complications. In this heterogeneous scenario, a non-systematic review of dose constraints for lung SBRT was performed, including the main organs at risk in the thorax.

Clinical results of stereotactic body radiotherapy (SBRT) in the treatment of isolated local recurrence of pancreatic cancer after R0 surgery: A retrospective study.

OBJECTIVE: To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. METHODS: A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI>18 months. No cases of acute G3 toxicity or greater occurred. CONCLUSIONS: SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.

Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study.

PURPOSE: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. RESULTS: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. CONCLUSION: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

High-quality Linac-based Stereotactic Body Radiation Therapy with Flattening Filter Free Beams and Volumetric Modulated Arc Therapy for Low-Intermediate Risk Prostate Cancer. A Mono-institutional Experience with 90 Patients.

AIMS: The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer. MATERIALS AND METHODS: Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate-specific antigen (PSA) ≤ 20 ng/ml, Gleason Score < 7, International Prostate Symptom Score < 7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life. RESULTS: Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment. CONCLUSIONS: Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life.

Utilidad clínica de la procalcitonina en gastroenteritis aguda / Use of procalcitonin as diagnostic marker in acute gastroenteritis

Introducción: No hay ningún marcador hematológico que diferencie con seguridad entre gastroenteritis aguda (GEA) bacteriana y no bacteriana. Nuestro objetivo fue evaluar la procalcitonina (PCT) como marcador de GEA de origen bacteriano y analizar su correlación con el ingreso hospitalario. Pacientes y Método: Estudio prospectivo de niños diagnosticados de GEA en el departamento de Urgencias durante un período de 7 meses que requirieron de analítica sanguínea y muestras de heces. Se analizaron variables epidemiológicas, clínicas y analíticas. Se excluyeron pacientes con enfermedad digestiva crónica, diarrea prolongada, inmunodeficiencia o tratamiento antibiótico previo. El estudio fue aprobado por el Comité de Ética y se solicitó consentimiento informado. Resultados: Se analizaron 45 pacientes. Los niños con GEA bacteriana tenían mayor edad (p = 0,027), mayor mediana de PCT y proteína C reactiva (PCR) (p = 0,001). Los valores de PCT y PCR que mejor discriminaron la etiología bacteriana fueron PCT > 0,5 mg/L (sensibilidad: 64,3 por ciento, especificidad: 83,9 por ciento, cociente de probabilidad positivo (CPP): 4) y PCR > 3 mg/dL (sensibilidad: 78,6 por ciento, especificidad: 90,3 por ciento, CPP: 8). No se encontró asociación entre la elevación de dichos marcadores y una mayor probabilidad de hospitalización. Conclusión: La procalcitonina, al igual que la PCR, se eleva en gastroenteritis bacterianas (p = 0,001), no siendo estos marcadores predictores de hospitalización.

Introduction: There is no hematological marker that reliably differentiates between bacterial and nonbacterial acute gastroenteritis (AGE). The objective of this study is to evaluate procalcitonin (PCT) as a marker for bacterial AGE and analyze its relationship with hospital admission. Patients and Method: A prospective study of children diagnosed with AGE was conducted at the emergency room during a period of seven months, which required blood and stool samples. Epidemiological, clinical and analytical variables were analyzed. Patients with chronic digestive disease, prolonged diarrhea, immunodeficiency or prior antibiotic treatment were excluded. The study was approved by the Ethics Committee and an informed consent was requested. Results: 45 patients were analyzed. Children with bacterial GEA were older (p = 0.027) and presented higher median PCT and C-reactive protein concentrations (CRP) (p = 0.001). The PCT and CRP values that best discriminated bacterial infection were PCT > 0.05 mg/L (sensibility 64.3 percent specificity 83.9 percent, positive probability coefficient (PPC): 4), and CRP > 3mg/dL (sensibility 78.6 percent, specificity 90.3 percent, PPC: 8). No association between the elevation of these markers and higher hospitalization probability was found. Conclusion: Procalcitonin, like CRP, is elevated in bacterial gastroenteritis (p = 0.001), but these markers are not a predictor of hospitalization.

Total monitor units influence on plan quality parameters in volumetric modulated arc therapy for breast case.

PURPOSE: To investigate the correlation between total monitor units (MU), dosimetric findings, and pre-treatment quality assurance for volumetric modulated arc therapy (VMAT) by RapidArc (RA). METHODS AND MATERIALS: Ten patients with breast cancer were considered. Dose prescriptions were: 48 Gy and 40.5 Gy in 15 fractions to, respectively, PTV(Boost) and PTVWholeBreast. A reference plan was optimized and four more plans using the "MU Objective", a tool for total MU controlling, were prepared imposing ± 20 and ± 50% total MU for inducing different complexities. Plan objectives were: D95% > 95% for both PTVs, and D2% < 107% for PTV(Boost); mean dose < 9.5 Gy and V20 Gy < 10% for ipsilateral lung; V18 Gy < 5% for heart; mean dose <3 Gy for controlateral breast; furthermore V5 Gy, V10 Gy, V20 Gy, and V30 Gy to body were minimized. Plans were evaluated in terms of technical parameters, dosimetric plan objectives findings and pre-treatment quality assurance (QA). RESULTS: Concerning PTVs, there were no significant differences for target coverage (D95%); mean doses for ipsilateral lung and controlateral breast, and V18 Gy for heart decreased with MUs increasing, reaching a plateau with reference plan. Body volume receiving low dose (V5-10 Gy) was minimized for reference plans. All plans had GAI (3 mm, 3%) > 95%. CONCLUSIONS: The data suggest that the best plan is the reference one, where the "MU Objective" tool was not used during optimisation. Nevertheless, it is advisable to use the "MU Objective" tool for re-planning when low GAI is found to increase its value. In this case, attention should be paid to OARs dose limits, since their values may be increased.

[Use of procalcitonin as diagnostic marker in acute gastroenteritis]. / Utilidad clínica de la procalcitonina en gastroenteritis aguda.

INTRODUCTION: There is no hematological marker that reliably differentiates between bacterial and nonbacterial acute gastroenteritis (AGE). The objective of this study is to evaluate procalcitonin (PCT) as a marker for bacterial AGE and analyze its relationship with hospital admission. PATIENTS AND METHOD: A prospective study of children diagnosed with AGE was conducted at the emergency room during a period of seven months, which required blood and stool samples. Epidemiological, clinical and analytical variables were analyzed. Patients with chronic digestive disease, prolonged diarrhea, immunodeficiency or prior antibiotic treatment were excluded. The study was approved by the Ethics Committee and an informed consent was requested. RESULTS: 45 patients were analyzed. Children with bacterial GEA were older (p=0.027) and presented higher median PCT and C-reactive protein concentrations (CRP) (p=0.001). The PCT and CRP values that best discriminated bacterial infection were PCT≥0.05 mg/L (sensibility 64.3%, specificity 83.9%, positive probability coefficient (PPC): 4), and CRP≥3 mg/dL (sensibility 78.6%, specificity 90.3%, PPC: 8). No association between the elevation of these markers and higher hospitalization probability was found. CONCLUSION: Procalcitonin, like CRP, is elevated in bacterial gastroenteritis (p=0.001), but these markers are not a predictor of hospitalization.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model.

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

Skin and cutaneous melanocytic lesion simulation in biomedical optics with multilayered phantoms.

The complex inner layered structure of skin influences the photon diffusion inside the cutaneous tissues and determines the reflectance spectra formation. Phantoms are very useful tools to understand the biophysical meaning of parameters involved in light propagation through the skin. To simulate the skin reflectance spectrum, we realized a multilayered skin-like phantom and a multilayered skin phantom with a melanoma-like phantom embedded inside. Materials used were Al(2)O(3) particles, melanin of sepia officinalis and a calibrator for haematology systems dispersed in transparent silicon. Components were optically characterized with indirect techniques. Reflectance phantom spectra were compared with average values of in vivo spectra acquired on a sample of 573 voluntary subjects and 132 pigmented lesions. The phantoms' reflectance spectra agreed with those measured in vivo, mimicking the optical behaviour of the human skin. Further, the phantoms were optically stable and easily manageable, and represented a valid resource in spectra formation comprehension, in diagnostic laser applications and simulation model implementation, such as the Monte Carlo code for non-homogeneous media.

Multispectral imaging and artificial neural network: mimicking the management decision of the clinician facing pigmented skin lesions.

Various instruments based on acquisition and elaboration of images of pigmented skin lesions have been developed in an attempt to in vivo establish whether a lesion is a melanoma or not. Although encouraging, the response of these instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and fluorescence imaging, cannot currently replace the well-established diagnostic procedures. However, in place of the approach to instrumentally assess the diagnosis of the lesion, recent studies suggest that instruments should rather reproduce the assessment by an expert clinician of whether a lesion has to be excised or not. The aim of this study was to evaluate the performance of a spectrophotometric system to mimic such a decision. The study involved 1794 consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions excised for histopathological diagnosis and 348 patients with 1940 non-excised lesions because clinically reassuring. Images of all these lesions were acquired in vivo with a multispectral imaging system. The data set was randomly divided into a train (802 reassuring and 1003 excision-needing lesions, including 139 melanomas), a verify (464 reassuring and 439 excision-needing lesions, including 72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions, including 76 melanomas). An artificial neural network (ANN(1)) was set up to perform the classification of the lesions as excision-needing or reassuring, according to the expert clinicians' decision on how to manage each examined lesion. In the independent test set, the system was able to emulate the clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462 correctly classified as excision-needing lesions, 72 (95%) were melanomas. No major variations in receiver operating characteristic curves were found between the test and the train/verify sets. On the same data set, a further artificial neural network (ANN(2)) was then architected to perform classification of the lesions as melanoma or non-melanoma, according to the histological diagnosis. Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be significantly better in the classification of reassuring lesions than ANN(2). This study suggests that multispectral image analysis and artificial neural networks could be used to support primary care physicians or general practitioners in identifying pigmented skin lesions that require further investigations.

Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms.

Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole. At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement). The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components. As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.