Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e.

OBJECTIVE: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. MATERIALS AND METHODS: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). RESULTS: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58-0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67-0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85-4.78) than without (4.14; SD: ±2.97; range: 2.18-5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08-32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14-48.72). CONCLUSIONS: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols.

A relevant long-term impact of the circulation of a potentially contaminated vaccine on the distribution of scrapie in Italy. Results from a retrospective cohort study.

A sudden increase in the incidence of scrapie in Italy in 1997 was subsequently linked to the use of a potentially infected vaccine against contagious agalactia. The relative risk for the exposed farms ranged between 6 and 40. The aim of this study was to assess the long-term impact of exposure to the potentially scrapie-contaminated vaccine on the Italian classical scrapie epidemic. We carried out a retrospective cohort study, fitting mixed-effects Poisson regression models, dividing national geographic areas into exposure categories on the basis of the vaccine circulation levels. We took into account the sensitivity of the surveillance system applied in the different areas. The population attributable fraction (PAF) was used to assess the impact on the total population of farms associated with the effect of circulation of the vaccine. The provinces where the vaccine was more often sold were noted to have a higher level of disease when compared to those provinces where the vaccine was sold less often (incidence rate ratio [IRR]: 2.7; 95% confidence interval [CI]: 1.1-6.5). The population attributable fraction was high (68.4%). Standardization techniques allowed to account for the potential of geographical variability in the sensitivity of the Italian surveillance system. Although the number of the directly exposed farms was limited, an important long-term impact of the vaccine circulation could be quantified in terms of secondary outbreaks likely due to the exchange of animals from directly exposed flocks.

Histidine at codon 154 of the prion protein gene is a risk factor for Nor98 scrapie in goats.

Prion protein gene (PRNP) polymorphisms are involved in modulating the appearance of atypical/Nor98 scrapie in sheep, with the alleles AHQ and AF141RQ strongly associated with occurrence of the disease. The presence of histidine at codon 154 has also been detected in Nor98-affected goats, but statistical analysis of the association between Nor98 and goat PRNP polymorphisms has not been reported previously. Here, a case-control study was carried out on eight Nor98-positive goats and 246 negative herdmates belonging to eight Italian Nor98 scrapie outbreaks. The results revealed that histidine at codon 154 is also strongly associated with the disease in goats.

Comparison of endorectal magnetic resonance imaging, clinical prognostic factors and nomograms in the local staging of prostate cancer patients treated with radiotherapy.

AIMS AND BACKGROUND: To determine retrospectively the role of endorectal magnetic resonance in the staging of prostate cancer. The aim of the study was to assess whether it is possible to identify a group of patients with prostate cancer, chosen for certain prognostic factors, eligible for radiotherapy that could take advantage of endorectal magnetic resonance in staging and therapy management. METHODS: Between January 2002 and December 2005, 143 patients with biopsy proven prostate cancer underwent endorectal magnetic resonance. All patients were initially evaluated considering the following prognostic factors: serum prostate-specific antigen at diagnosis, Gleason score, histological grade, involvement of the seminal vesicle and extracapsular extension using the Roach III and ECE equations. The findings were then compared to the results of endorectal magnetic resonance. RESULTS: The relationship between the variable post-endorectal magnetic resonance stage modification and Gleason score was statistically significant (P = 0.02847). In addition, our study showed a statistically significant correlation between the risk of seminal vesicle involvement according to the Roach III formula and post-endorectal magnetic resonance stage modification (P = 0.01305). Conversely, statistical analysis showed no significant correlation between post-endorectal magnetic resonance stage modification and prostate-specific antigen values (P = 0.83440) or between post-endorectal magnetic resonance stage modification and the risk of extracapsular extension according to the extracapsular extension formula (P = 0.42748). CONCLUSIONS: Our data suggest that endorectal magnetic resonance could be used for staging of the subgroup of patients at high risk of seminal vesicle involvement (> 15%). Although we found a statistical correlation between Gleason score and post-endorectal magnetic resonance stage modification, statistical analysis showed no correlation between any of the subgroups. Therefore, it is not possible at the moment to identify a subgroup of patients by Gleason score that may benefit from endorectal magnetic resonance. In our opinion, extracapsular extension values were not useful to select patients for endorectal magnetic resonance.

Accessibility as a major determinant of radiotherapy underutilization: a population based study.

BACKGROUND AND PURPOSE: A survey was conducted of radiotherapy (RT) resources and utilization in a northwestern Italian Region in order to assess geographical variations in radiotherapy utilization rates, and the effects of infrastructure supply on accessibility. MATERIALS AND METHODS: The survey was conducted by analysing standardized utilization rates based on administrative records. The data were analysed at both Regional and Local Health Unit (LHU) level. RESULTS: Wide variation was found among LHUs RT utilization rates--the sex- and age-standardized rates varied from 1.8/1000 inhabitants to more than 3/1000 inhabitants. Patients resident in LHUs with no RT service showed a lower probability of accessing RT (standardized rate ratio (SRR), 0.82; 95%IC, 0.80-0.85). The utilization rate decreased in relation to the distance between a patient's residence and the nearest RT service; the reduction was greater for patients > or =70 years of age. CONCLUSION: The wide geographic variation implies lack of equity in access to services. Utilization levels decreased significantly with increasing distance from the nearest RT service, distance being a barrier to access particularly for older persons. The heterogeneous distribution of services on the Regional territory seems a relevant explanation of differences in utilization rates.

Assessment of clinical criteria to diagnose scrapie in Italy.

A reliable ante-mortem test for the detection of scrapie in all genotypes has not yet been developed and clinical diagnosis remains a useful tool for surveillance purposes. This paper describes the results of a three-year study in which clinical signs consistent with scrapie were recorded according to standardized criteria in 245 sheep from 21 outbreaks in Italy in order to identify helpful criteria for the diagnosis of the disease. Thirty-seven sheep were scrapie-positive at post-mortem rapid testing, 23 showed weight loss, 20 had proprioceptive deficits, 17 demonstrated ataxia and nibble reflex, and some sheep had a combination of signs. Six scrapie-positive sheep were asymptomatic. The clinical protocol was easy to handle and appears to be a useful tool for improving passive surveillance. The data suggested that positive clinical history, nibble, and nibble combined with proprioceptive positioning deficit have a quite high negative predictive value. The protocol will be proposed as a tool for field inspection in passive surveillance in Italy.

Combining independent studies of diagnostic fluorodeoxyglucose positron-emission tomography and computed tomography in mediastinal lymph node staging for non-small cell lung cancer.

AIMS AND BACKGROUND: A meta-analysis of diagnostic test performance was conducted to compare the results of relevant studies reporting diagnostic accuracy values for mediastinal staging in patients with non-small cell lung cancer (NSCLC). This paper deals with the two most accurate imaging techniques currently in use: positron emission tomography (PET) with FDG and computed tomography (CT). A statistical pooling method was used to perform a quantitative meta-analysis aimed at demonstrating the potential advantage of one of these two methods. METHODS: Studies in all languages published between 1998 and 2005 that examined the use of FDG-PET and CT for mediastinal staging in NSCLC patients, enrolled at least 18 participants, and provided enough data to allow calculation of sensitivity and specificity rates were considered eligible for the quantitative meta-analysis. Statistical methods to pool the overall estimates of sensitivity and specificity and to compare the discriminant power of PET and CT were discussed and used. RESULTS: Of the 13 studies included in the analysis, 12 reported greater accuracy of FDG-PET than CT in detecting mediastinal lymph node metastases. The sensitivity of FDG-PET ranged from 50% to 100%. The estimate of the overall sensitivity was 0.83% with 95% CI (0.749-0.913). Specificity ranged from 79% to 100%, with an overall estimated specificity of 0.87% with 95% CI (0.80-0.95). For CT, the sensitivity and specificity ranged from 50% to 97% and 58% to 94%, respectively; the overall estimate was 0.68% with 95% CI (0.582-0.788) and 0.76% with 95% CI (0.668-0.859). The summary receiver operating characteristic (SROC) approach was used to assess the superior diagnostic accuracy of one of the two methods. The areas under the two SROC curves were AUC(PET) = 0.909 vs. AUC(CT) = 0.794. CONCLUSIONS: Numerical and visual results of the meta-analysis of recent relevant reports agreed that FDG-PET is more accurate than CT in identifying mediastinal lymph node metastases in non-small cell lung cancer.

[Use of discharge records to define the oncological diagnoses for outpatient radiotherapy patients]. / Identificazione della diagnosi oncologica di pazienti trattati presso servizi ambulatoriali di radioterapia attraverso link con le schede di dimissione ospedaliera.

OBJECTIVE: Outpatient activity recording system has a potential role in clinical practice evaluation. Nevertheless, up to now, its utilisation has been limited by the paucity of its clinical data. This study describes a procedure for identifying the oncological diagnosis in patients receiving radiotherapy at an ambulatory service in the Piedmont Region. The procedure is based on the record linkage between discharge records (SDO) and outpatients records (PA), in order to obtain clinical information from the diagnosis related to possible admissions of the patients. METHODS: The study analyzed radiotherapy outpatients records in 2003 related to Piedmont residents and all discharge records in years 2000-2004. The quality of the procedure has been assessed by using the information on the real oncological diagnosis as reported in the outpatients medical records of a random sample of patients. RESULTS: The record linkage with SDO allows to define an oncological diagnosis for 82% (95% CI 78.5-84.8) of the patients. Agreement between defined diagnosis and the real one is 85.7% (CI 95% 82.2-88.6). The validity of the procedure is affected by the patients' cancer site. The distribution by cancer site of the patients treated with radiotherapy in Piedmont Region obtained with the record linkage procedure is homogeneous to the real distribution of the random sample used for control. CONCLUSIONS: Overall, the record linkage between SDO and radiotherapy PA shows a good performance in defining the oncological diagnosis of the patients receiving radiotherapy at an ambulatory setting. This method allows to increase interest and utility of PA records.

Protein osmotic pressure and cross-bridge attachment determine the stiffness of thin filaments in muscle ex vivo.

The properties of some models of the actin filament are compared with those of the thin filament in muscle. The greater stiffness of thin filaments ex vivo with respect to F-actin in vitro is attributed to the effect of both protein osmotic pressure and the attached cross-bridges. By comparing the stiffness of thin filaments in vitro and in isometric and rigor muscles the stiffness of thin filaments in relaxed muscle is computed. The upper limit of thin filament stretching is deduced to approach approximately 10 nm microm(-1). It is also calculated that, on stretching by 2.02 nm of the fully non-overlapped thin filament or by 1.59 nm of the thin filament on isometric contraction, the energy released on the hydrolysis of one molecule of ATP is fully used up.

Viscosity as an inseparable partner of muscle contraction.

A simple model is presented where, by an iterative procedure, the forces delivered by the power strokes are summed up to overcome the load. The system is moderated by the viscous hindrance. The model reproduces the features of muscle contraction as defined by the data of He et al. [1997. ATPase kinetics on activation of permeabilized isometric fibres from rabbit and frog muscle: a real time phosphate assay. J. Physiol. 501, 125-148] on rabbit psoas muscle fibres. According to the model power strokes are random. Energy summation take place if the subsequent power stroke occurs before the energy delivered by the previous power stroke is completely used. In order the sarcomere to be competent to contract initial driving force must reach a threshold whose value increases with the load. The step size of the power stroke decreases with the increase of the load. The viscous regime is simulated by the equation, where 1/k measures the viscous hindrance of the system. The relationship between water activity, viscosity and stiffness is discussed. It is concluded that the three parameters vary cyclically and that when water activity decreases (sarcomere shortening, cross-bridge attachment) viscosity and stiffness increase.

Are quality indicators for radiotherapy useful in the evaluation of service efficacy in a new based radiotherapy institution?

AIMS AND BACKGROUND: A number of documents assess the need for quality assurance in radiotherapy, which must be constantly monitored and possibly improved. In this regard, a system that confirms the quality of a department has been suggested and quality indicators have been used to improve the quality of the service. The National Health Service (Istituto Superiore di Sanità) approved a National Research Project to increase the quality of radiotherapy. The aim of the present study was to analyze the practical feasibility and efficacy of the quality indicators elaborated by the National Health Service study group in a radiotherapy unit. PATIENTS AND METHODS: The voluntary accredited program was carried out by the Radiotherapy Department of IRCC in Candiolo from June to August 2002. We analyzed 8 of the 13 indicators according to the National Health Service Project. For this purpose, 133 consecutive patients treated in our Unit were analyzed, and the results are reported according to the appropriate indicator (number of staff related to patients treated, waiting list, case history accuracy, multidisciplinary approach, number of treatment plans performed by CT, number of fields per fraction, number of portal imaging performed per overall treatment, and patient satisfaction). RESULTS: The number of professional staff related to the number of patients treated was easy to calculate and it could be the basis for further evaluation. The overall waiting time was 55.4 days, and it changed for different radiotherapy goals. We obtained 80% conformity in case-history accuracy. The number of multidisciplinary consultations performed ranged between 50% and 100%. The number of CT plans was about 1.6 +/- 0.9 plans per patient. The mean number of fields performed per day and per patient is 3.5 +/- 1.7 and was in agreement with the fact that more than 50% of treatments in our Center were performed with conformal radiotherapy. An average of 16.7 +/- 10.0 portal imaging per case was performed. The percentage of patient satisfaction with the staff obtained a very high compliance. CONCLUSIONS: The self evaluation promoted by the National Health Service Project allows the monitoring of the activities of the service in order to asses critical factors and it can be the starting point to improve the quality of the service and to compare national and international quality assurance results.

Cooperative behaviour of the elementary sarcomere units and the cross-bridge step size.

We present a model of muscle contraction based on purely physical grounds and modulated by a parameter, k, related to the visco-elastic hindrances of the contractile apparatus. The model predicts a strong cooperation among sarcomere units and proposes that viscous hindrance is a fundamental component of the economy of the contraction. The concept of cross-bridge step size is also discussed and it is concluded that the step size is of various and probably undeterminable length.

The transition of polymers into a network of polymers alters per se the water activity.

We have found that polyacrylamide gels cross-linked with bisacrylamide induce a larger macromolecular osmotic pressure than the non cross-linked gels. This means also that in the cross-linked gels hydration water is held more tightly to the polymer, i.e., more work is needed to remove water, than in the non cross-linked gel. Since the chemical nature of the two gels is extremely similar, we propose that the formation of the network alters per se the water activity.

Is one Gy always one Gy? The integration between conventional radiotherapy and special techniques.

The new radiotherapy techniques as HDR and LDR brachytherapy, stereotactic radiotherapy, 3D-CRT, and IMRT require an accurate knowledge of the biological characteristics of the tumor with correct definition of target volumes. As demonstrated by the two reported cases, the formulae equivalent to 2 Gy in the special techniques are useful for the increase in the total dose to GTV while sparing the organs at risk.