Modelling bodyweight to avoid anthelmintic underdosing of goats in resources-limited settings.

Improved management of livestock in resource-limited settings can provide a means towards improved human nutrition and livelihoods. However, gastrointestinal nematodes (GIN) are a significant production-limiting factor. Anthelmintics play a role in GIN management; however, few anthelmintic classes are available in many low-middle-income countries. Utilising a limited range of classes may increase selection for anthelmintic resistance; therefore, strategies to reduce other selective pressures are of heightened importance. Avoiding anthelmintic underdosing is one such strategy, but it can be challenging without access to accurate bodyweight measurement. Many previous studies have used thoracic girth as a practical proxy for bodyweight in goats; however, they have rarely considered the potential impact of natural variation on therapeutic doses. Here, the relationship between bodyweight and thoracic girth was modelled using data from 820 goats from three Malawian biomes in two seasons, with the specific aim of avoiding underestimation of bodyweight. The internally cross-validated linear regression (∛Weight ~ 0.053 + 0.040*Girth, R2 = 0.92, rounded up to the nearest 5 kg) was validated against data from an additional 352 Malawian goats (1.4% of goats allocated an underdose and 10.2% allocated a dose > 200% of bodyweight). The equation was further externally validated using an historical dataset of 150 goats from Assam, India (2.7% of goats were allocated to an underdose and 24.8% allocated to a > 200% of bodyweight). These results suggest that a more globally generalisable approach may be feasible, provided the accuracy of the estimate is considered alongside the therapeutic index of the pharmaceutical.

Elimination of human rabies in Goa, India through an integrated One Health approach.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.

Conjunctival mucous membrane colour as an indicator for the targeted selective treatment of haemonchosis and of the general health status of peri-urban smallholder goats in southern Malawi.

The world's growing population is becoming increasingly centred around large cities, affording opportunities for peri-urban food production. Goats are well-suited to conversion of resources that are available in peri-urban settings into meat and occasionally milk. Haemonchus contortus has been described as "the nemesis of small ruminant production systems in tropical and subtropical regions"; hence control of haemonchosis through planned animal health management affords a pragmatic first step in improving the production efficiency of peri-urban goats. This study of peri-urban goat production investigated the potential value of targeted selective treatment of haemonchosis. 452 peri-urban goat keepers in southern Malawi were visited during three seasonal periods with relevance to the epidemiology of haemonchosis. 622, 599 and 455 individually identified goats were clinically examined during the dry season, the rainy season, and shortly after the end of the rainy season, respectively. Data were recorded for sex, age, weight, conjunctival mucous membrane colour score (FAMACHA©), body condition score (BCS) and faecal worm egg count (FEC); and where possible for pregnancy and lactation status. Animals with pale ocular mucous membranes were treated with 10 mg/kg albendazole, then re-examined 14 days later. Animals with pink mucous membranes, but FECs ≥250 eggs per gram were also re-examined and treated 14 days later. The results show high variability in growth rates deduced from the ages and bodyweights of each of 999 goats at the time of their enrolment. FAMACHA© scores alone were a poor index for the targeted selective treatment of haemonchosis, because they failed to identify too many animals that would have required treatment at different times of year and using different FAMACHA© and FEC cut-offs. Combining the indices of FAMACHA© scores ≥4, body condition scores ≥2, and age >18 months was more reliable in identifying those animals requiring treatment when different epidemiologically-relevant FEC thresholds for different seasons were taken into account. Inclusion of late pregnancy or early lactation status would have resulted in very few animals requiring treatment being missed. The use of conjunctival mucous membrane colour scoring in this way provided a valuable insight of the general health status of the peri-urban goats, to create opportunities for planned animal health management to improve productivity. The efficacy of albendazole treatment was poor, putatively due to drug resistance, or poor drug bioavailability in goats. In summary, our study shows opportunities for better production efficiency in peri-urban goats, and demonstrates the value of simple clinical diagnostic indices as decision support tools in planned animal health management.

1H, 13C, and 15N backbone chemical shift assignments of coronavirus-2 non-structural protein Nsp10.

The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins and will provide NMR chemical shift assignments of the molecular components of this virus. The SARS-CoV-2 genome encodes approximately 30 different proteins. Four of these proteins are involved in forming the viral envelope or in the packaging of the RNA genome and are therefore called structural proteins. The other proteins fulfill a variety of functions during the viral life cycle and comprise the so-called non-structural proteins (nsps). Here, we report the near-complete NMR resonance assignment for the backbone chemical shifts of the non-structural protein 10 (nsp10). Nsp10 is part of the viral replication-transcription complex (RTC). It aids in synthesizing and modifying the genomic and subgenomic RNAs. Via its interaction with nsp14, it ensures transcriptional fidelity of the RNA-dependent RNA polymerase, and through its stimulation of the methyltransferase activity of nsp16, it aids in synthesizing the RNA cap structures which protect the viral RNAs from being recognized by the innate immune system. Both of these functions can be potentially targeted by drugs. Our data will aid in performing additional NMR-based characterizations, and provide a basis for the identification of possible small molecule ligands interfering with nsp10 exerting its essential role in viral replication.

1H, 13C, and 15N backbone chemical shift assignments of the apo and the ADP-ribose bound forms of the macrodomain of SARS-CoV-2 non-structural protein 3b.

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.

Implementation of high coverage mass rabies vaccination in rural Uganda using predominantly static point methodology.

Despite successful eradication programmes in many regions, rabies remains responsible for approximately 60,000 human deaths annually, and no country in Africa is rabies-free. Dogs are the principal reservoir of the virus in Africa and the World Health Organisation recommends that at least 70% of the dog population be vaccinated in order to break the transmission cycle. Most attempts at mass rabies vaccinations in Africa have failed to vaccinate high numbers of dogs at a high coverage. Successful studies have often used a door-to-door (DTD) approach, which is logistically challenging and expensive compared to a static point (SP) approach. Mission Rabies has successfully implemented a combined SP and DTD method in cities in India and Malawi. This campaign used a combined methodology in rural Uganda, starting with a SP campaign, followed by a DTD campaign, and then subsequent transect surveys to assess vaccination coverage. This was facilitated by the use of a smartphone application which recorded all vaccinations and survey responses along with their Global Positioning System location. A total of 4172 dogs were vaccinated in 7 days, attaining an estimated 88.4% coverage. This campaign is of particular note as 95.9% of the vaccinations were performed at SPs. The human-to-dog ratio was 4.9 with a mean dogs per house of 1.2. Most dogs were owned (93.7%). This demonstrates that high-number, high-coverage vaccination is achievable in rural Uganda and provides data that may refine future campaign approaches.

Macroscopic locoregional relapse from prostate cancer: which role for salvage radiotherapy?

INTRODUCTION: Salvage radiotherapy (SRT) after radical prostatectomy for prostate cancer (PCa) is recommended as soon as PSA rises above 0.20 ng/ml, but many patients (pts) still experience local macroscopic relapse. The aim of this multicentric retrospective analysis was to evaluate the role of SRT in pts with macroscopic relapse. MATERIALS AND METHODS: From 2001 to 2016, 105 consecutive pts with macroscopic PCa relapse underwent SRT ± androgen deprivation therapy (ADT). Mean age was 72 years. At time of relapse, 29 pts had a PSA value < 1.0 ng/mL, 50 from 1.1 to 5, and 25 pts > 5. Before SRT, 23 pts had undergone 18F-choline PET and 15 pts pelvic MRI. Ninety-four pts had prostatic bed relapse only, and four nodal involvement. Fifty-one pts were previously submitted to first-line ADT, while 6 pts received ≥ 2 lines. RESULTS: At a median follow-up of 52 months, 89 pts were alive, while 16 were dead. Total RT dose to macroscopic lesions was > 70 Gy in 58 pts, 66-70 Gy in 43, and < 66 Gy in 4 pts. In 72 pts, target volume encompassed only the prostatic bed with sequential boost to macroscopic site; 33 pts received prophylactic pelvic RT. Ten-year overall survival was 76.1%, while distant metastasis-free survival was 73.3%. No grade 4-5 toxicities were found. CONCLUSIONS: SRT ± ADT for macroscopic relapse showed a favorable oncological outcome supporting its important role in this scenario. Data from this series suggest that SRT may either postpone ADT or improve results over ADT alone in appropriately selected pts.

Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

La rage est l'une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l'Antarctique est indemne de tout lyssavirus mais cette hypothèse n'est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l'ont révélé le foyer historique survenu à Guam ainsi que l'arrivée de chauves-souris enragées à Hawaï. L'Australie est le seul continent habité où la rage ne sévit pas à l'état enzootique, le virus de la rage y étant absent. L'Europe et l'Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l'Ancien Monde. L'élimination de la rage humaine transmise par les chiens à l'horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l'expérience acquise tout au long du xxe siècle.

La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo¼. La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.

Global rabies management: perspectives on regional strategies for prevention and control.

Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir. Elimination of human rabies mediated by dogs may be feasible, based upon the elicitation of herd immunity, the application of sound health economic principles for appropriate disease management and technology transfer to those developing countries where rabies is hyper-endemic. Global canine rabies elimination has clear benefits for public health, veterinary medicine and conservation biology, so these sectors must collaborate using a transdisciplinary 'One Health' approach that allows the creation of long-term regional strategies for enhanced surveillance and practical intervention.

La rage est une maladie zoonotique majeure, qui demeure négligée malgré l'existence de tests de diagnostic hautement sensibles et de vaccins efficaces chez l'homme comme chez l'animal. La persistance de la rage chez de nombreuses espèces de carnivores sauvages et de chauves-souris et la diversité des espèces de Lyssavirus continuent de poser des difficultés en termes de prévention et de lutte contre la maladie. Néanmoins, le fardeau mondial de la rage peut être considérablement réduit en pratiquant la vaccination massive des chiens, ces derniers constituant le principal réservoir. L'élimination de la rage transmise par les chiens est un objectif atteignable si l'on s'appuie sur des concepts solides en matière d'immunité à l'échelle des troupeaux, d'économie de la santé et de transfert technologique, tout en apportant des bénéfices mutuels accrus pour la santé publique, la médecine vétérinaire et la biologie de la conservation grâce à la mise en oeuvre d'une approche régionale pour la surveillance, les interventions, la certification et la collaboration pluridisciplinaire dans un contexte Une seule santé.

La rabia es una importante enfermedad zoonótica desatendida, y ello pese a que existen pruebas de diagnóstico de gran sensibilidad y vacunas de contrastada eficacia en personas y animales. La perpetuación de la rabia en múltiples especies de carnívoros silvestres y murciélagos y la presencia de diversos lisavirus siguen dificultando el trabajo de prevención y control de la enfermedad. Con todo, cabe reducir buena parte de la carga mundial que impone la rabia mediante la vacunación masiva de perros, que son su principal reservorio. Si se aplican conceptos sólidos en materia de inmunidad de rebaño, economía de la salud y transferencia de tecnología, abordando las labores de vigilancia, intervención, certificación y colaboración multidisciplinar desde una lógica regional y desde los postulados de «Una sola salud¼, la eliminación de la rabia humana transmitida por perros puede ser un objetivo factible y muy beneficioso para la salud pública, la medicina veterinaria y la biología de la conservación.

The problem of stray dogs.

The effective management of stray dogs is critically important in any rabies vaccination programme. In many rabies-endemic countries, stray dogs represent a significant proportion of both the free-roaming and total dog populations, and to ensure that rabies elimination programmes are successful, it is essential that this portion of the dog population (stray dogs) is vaccinated at high coverage. However, there are a number of challenges to managing and delivering rabies vaccinations to stray dogs. This paper will review the most pertinent issues relating to the problem of stray dogs and rabies elimination, focusing on the challenges relating to the estimation of population size, vaccination administration and vaccine coverage assessment in stray dog populations. The authors will highlight how these challenges can be overcome, notably by reviewing the census techniques that have been employed to assess stray dog populations, which then facilitate the planning and design of vaccination programmes. In addition, they discuss the range of vaccination strategies that are available and that have been used to vaccinate stray dogs and review how vaccination coverage can be assessed in this population. Finally, the benefits of population management in stray dogs through neutering programmes are reviewed. In short, this paper highlights the importance of ensuring that stray dogs, as well as owned dogs, are included in vaccination programmes and emphasises that many of the challenges related to protecting stray dogs from rabies can be overcome.

L'efficacité de la gestion des populations de chiens errants est un aspect essentiel de tout programme de vaccination contre la rage. Dans de nombreux pays où la rage est endémique, les chiens errants constituent un segment important des populations de chiens laissés en liberté et plus généralement de la population canine totale, de sorte que le succès des programmes d'élimination de la rage repose sur l'impératif d'assurer une forte couverture vaccinale au sein de cette partie de la population canine. Toutefois, s'agissant des chiens errants la gestion de la vaccination et l'administration des vaccins antirabiques présentent des difficultés particulières. Les auteurs font le point sur les principales questions posées par la problématique des chiens errants dans une perspective d'élimination de la rage, qui concernent notamment la difficulté d'évaluer la taille des populations concernées, d'administrer les vaccins dans ce cadre et d'évaluer la couverture vaccinale obtenue. Les auteurs soulignent les réponses qui peuvent être apportées à ces problèmes, en particulier en revoyant les techniques de recensement appliquées jusqu'à présent pour évaluer les populations de chiens errants, ce qui permettra ensuite de faciliter la planification et la conception des programmes de vaccination. En outre, ils examinent les différentes stratégies de vaccination mises en oeuvre en la matière et font le point sur les moyens d'évaluer la couverture vaccinale de ces populations. Enfin, ils analysent les avantages apportés par les programmes de stérilisation pour maîtriser les populations de chiens errants. En résumé, cet article met l'accent sur l'importance d'inclure les chiens errants au même titre que les chiens ayant un maître dans les programmes de vaccination et souligne que la plupart des difficultés liées à la protection des chiens errants contre la rage peuvent être résolues.

Uno de los aspectos capitales de todo programa de vacunación antirrábica es la gestión eficaz de las poblaciones de perros vagabundos. En muchos países con rabia endémica, estos perros representan un porcentaje sustancial tanto de la población canina total como de los perros en libertad. El éxito de todo programa de eliminación de la rabia pasa necesariamente por lograr una elevada cobertura de vacunación en este segmento de la población canina (los perros vagabundos). Sin embargo, la gestión y la vacunación antirrábica de los perros vagabundos presentan una serie de dificultades. Los autores pasan revista a los aspectos que más inciden en el problema de los perros vagabundos y la eliminación de la rabia, prestando especial atención a las dificultades que presentan la estimación del tamaño de la población, la administración de vacunas y el cálculo de la cobertura de vacunación de las poblaciones de perros vagabundos. Después explican la manera de superar estas dificultades, en particular describiendo las técnicas de censo empleadas para calcular el tamaño de las poblaciones, lo que a su vez facilita la concepción y planificación de programas de vacunación. Además, describen el arsenal existente de procedimientos de vacunación que se han utilizado para vacunar a los perros vagabundos y explican cómo estimar en estas poblaciones la cobertura de vacunación. Por último exponen los beneficios de gestionar las poblaciones de perros vagabundos con programas de esterilización. En resumidas cuentas, los autores recalcan aquí la importancia de que los programas de vacunación canina lleguen a los perros vagabundos, y no solo a los animales con dueño, e insisten en que muchos de los problemas que se plantean para proteger de la rabia a los perros vagabundos tienen solución.

A machine learning tool for re-planning and adaptive RT: A multicenter cohort investigation.

PURPOSE: To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. MATERIALS AND METHODS: 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier. RESULTS: The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases. CONCLUSIONS: SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis.

A novel surface imaging system for patient positioning and surveillance during radiotherapy. A phantom study and clinical evaluation.

BACKGROUND: The use of optical surface positioning to support or replace X-ray-based image-guided radiotherapy (IGRT) may reduce patient exposure to extra dose. In specifically designed phantom tests, we analyzed the potential of a new scanning device preclinically. The system's clinical performance was evaluated in comparison to cone-beam computed tomography (CBCT) in a prospective study. MATERIALS AND METHODS: We first evaluated the scanning performance in terms of accuracy and reproducibility using phantom tests. An institutional review board (IRB)-approved clinical evaluation encompassing 224 fractions in 13 patients treated in three different regions (head and neck, thorax, pelvis) was then performed. Patients were first positioned using CBCT and then scanned with the Catalyst(TM) (C-RAD, Uppsala, Sweden) optical system to define the resulting difference vector. RESULTS: Individual system settings are necessary for different scanning conditions. Reproducibility tests with phantoms showed a mean difference of 0.25 ± 0.21 cm. Accuracy tests showed a mean difference of less than 0.52 ± 0.41 cm. Considering all patients, clinical data showed residual target position differences between Catalyst(TM) (surface-driven) and CBCT (target-driven) systems within 0.07 ± 0.28 cm/- 0.13 ± 0.40 cm/0.15 ± 0.36 cm/0.11 ± 1.57°/- 0.43 ± 1.68/- 0.10 ± 1.67° (lateral/longitudinal/vertical/rotation/roll/pitch). CONCLUSION: Scanning quality depends on the color and shape of the scanned surface. Upon prospective clinical evaluation, excellent agreement between target- and contour driven positioning was observed. Catalyst(TM) may reduce CBCT scan frequency in patients where tumor location is fixed relative to the surface.

Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer.

PURPOSE: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. PATIENTS AND METHODS: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. CONCLUSION: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

Clinical evaluation of a commercial surface-imaging system for patient positioning in radiotherapy.

BACKGROUND: Laser scanning-based patient surface positioning and surveillance may complement image-guided radiotherapy (IGRT) as a nonradiation-based approach. We investigated the performance of an optical system compared to standard kilovoltage cone-beam computed tomography (CBCT) and its potential to reduce the number of daily CBCTs. PATIENTS AND METHODS: We analyzed the patient positioning of 153 treatment fractions in 21 patients applied to three different treatment regions. Patients were first scanned with CBCT, shifted to the optimal isocenter position, and an optical scan was performed to verify the matching in relation to CBCT. RESULTS: For the head-and-neck region, the lateral/longitudinal/vertical/rotational/roll and pitch shift was 0.9 ± 1.8 mm/-2.7 ± 3.8 mm/-0.8 ± 3.6 mm/0.0 ± 1.1°/-0.5 ± 2.1°/0.2 ± 1.6°. For the thorax, the lateral/longitudinal/vertical/roll and pitch shift was -1.2 ± 3.6 mm/0.8 ± 5.1 mm/0.8 ± 4.3 mm/0.6 ± 1.4°/0.1 ± 0.9°/0.3 ± 1.0°. For the pelvis, the respective values were -2.5 ± 4.1 mm/4.6 ± 7.3 mm/-5.1 ± 7.4 mm/0.3 ± 1.1°/-0.5 ± 1.0°/0.3 ± 2.1°. In total, the recorded disagreement was -1.0 ± 3.6 mm/1.0 ± 6.3 mm/-1.8 ± 5.9 mm/0.3 ± 1.2°/-0.3 ± 1.5°/0.2 ± 1.7°. CONCLUSION: This analysis showed good agreement between the optical scanner approach and CBCT. The optical system holds potential to ensure precise patient positioning and reduced CBCT frequency in tumor locations with fixed relation to surface structures.

Assessment of renal function after conformal radiotherapy and intensity-modulated radiotherapy by functional 1H-MRI and 23Na-MRI.

PURPOSE: Adjuvant radiochemotherapy (RCHT) improves survival of patients with locally advanced gastric cancer. Conventional three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to a significant amount of the left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) provides excellent target coverage with improved kidney sparing. Few long-term results on IMRT for gastric cancer, however, have been published. Functional magnetic resonance imaging (fMRI) at 3.0 T including blood oxygenation-level dependent (BOLD) imaging, diffusion-weighted imaging (DWI) and, for the first time, (23)Na imaging was used to evaluate renal status after radiotherapy with 3D-CRT or IG-IMRT. PATIENTS AND METHODS: Four disease-free patients (2 after 3D-CRT and 2 after IMRT; FU for all patients > 5 years) were included in this feasibility study. Morphological sequences, axial DWI images, 2D-gradient echo (GRE)-BOLD images, and (23)Na images were acquired. Mean values/standard deviations for ((23)Na), the apparent diffusion coefficient (ADC), and R2* values were calculated for the upper/middle/lower parts of both kidneys. Corticomedullary (23)Na-concentration gradients were determined. RESULTS: Surprisingly, IG-IMRT patients showed no morphological alterations and no statistically significant differences of ADC and R2* values in all renal parts. Values for mean corticomedullary (23)Na-concentration matched those for healthy volunteers. Results were similar in 3D-CRT patients, except for the cranial part of the left kidney. This was atrophic and presented significantly reduced functional parameters (p = 0.001-p = 0.033). Reduced ADC values indicated reduced cell density and reduced extracellular space. Cortical and medullary R2* values of the left cranial kidney in the 3D-CRT group were higher, indicating more deoxygenated hemoglobin due to reduced blood flow/oxygenation. ((23)Na) of the renal cranial parts in the 3D-CRT group was significantly reduced, while the expected corticomedullary (23)Na-concentration gradient was partially conserved. CONCLUSIONS: Functional MRI can assess postradiotherapeutic renal changes. As expected, marked morphological/functional effects were observed in high-dose areas (3D-CRT), while, unexpectedly, no alteration in kidney function was observed in IG-IMRT patients, supporting the hypothesis that reducing total/fractional dose to the renal parenchyma by IMRT is clinically beneficial.

Clinical relevance of different dose calculation strategies for mediastinal IMRT in Hodgkin's disease.

BACKGROUND AND PURPOSE: Conventional algorithms show uncertainties in dose calculation already for three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) might even increase these. We wanted to assess differences in dose distribution for pencil beam (PB), collapsed cone (CC), and Monte Carlo (MC) algorithm for both 3D-CRT and IMRT in patients with mediastinal Hodgkin lymphoma. PATIENTS AND METHODS: Based on 20 computed tomograph (CT) datasets of patients with mediastinal Hodgkin lymphoma, we created treatment plans according to the guidelines of the German Hodgkin Study Group (GHSG) with PB and CC algorithm for 3D-CRT and with PB and MC algorithm for IMRT. Doses were compared for planning target volume (PTV) and organs at risk. RESULTS: For 3D-CRT, PB overestimated PTV(95) and V(20) of the lung by 6.9% and 3.3% and underestimated V(10) of the lung by 5.8%, compared to the CC algorithm. For IMRT, PB overestimated PTV(95), V(20) of the lung, V(25) of the heart and V(10) of the female left/right breast by 8.1%, 25.8%, 14.0% and 43.6%/189.1%, and underestimated V(10) of the lung, V(4) of the heart and V(4) of the female left/right breast by 6.3%, 6.8% and 23.2%/15.6%, compared to MC. CONCLUSION: The PB algorithm underestimates low doses to the organs at risk and overestimates dose to PTV and high doses to the organs at risk. For 3D-CRT, a well-modeled PB algorithm is clinically acceptable; for IMRT planning, however, an advanced algorithm such as CC or MC should be used at least for part of the plan optimization.

[Rules and regulations applying to incidents in radiotherapy]. / Rechtliche Grundlagen für den Umgang mit sicherheitsrelevanten Ereignissen in der Strahlentherapie.

AIMS AND PURPOSE: Radiotherapy is an essential and reliable element of the treatment armamentarium in oncology. Numerous rules, regulations, and protocols minimize the associated risks. It can, however, never be excluded that errors in the treatment delivery chain result in inadequate tumor doses or unnecessary damage to organs at risk. A legal framework governs the management of such incidents. The most important European and North American regulations are reported. RESULTS: Various directives issued by the European Union are differently implemented nationally. This applies particularly to the characterization of incidents that must be reported to authorities. Reporting thresholds, audit systems, and the extent of the integration of voluntary reporting systems vary. CONCLUSION: Radiotherapy incidents are dealt with differently on an international level. Changes are to be expected based on the European Basic Safety Standards Directive that is currently being prepared and will have to be implemented nationally in due course.

[Image-guided radiation therapy]. / Bildgeführte Strahlentherapie.

Radiotherapy technology has improved rapidly over the past two decades. New imaging modalities, such as positron emission (computed) tomography (PET, PET-CT) and high-resolution morphological and functional magnetic resonance imaging (MRI) have been introduced into the treatment planning process. Image-guided radiation therapy (IGRT) with 3D soft tissue depiction directly imaging target and normal structures, is currently replacing patient positioning based on patient surface markers, frame-based intracranial and extracranial stereotactic treatment and partially also 2D field verification methods. On-line 3D soft tissue-based position correction unlocked the full potential of new delivery techniques, such as intensity-modulated radiotherapy, by safely delivering highly conformal dose distributions that facilitate dose escalation and hypofractionation. These strategies have already resulted in better clinical outcomes, e.g. in prostate and lung cancer and are expected to further improve radiotherapy results.