Mobilising Expertise and Resources to Close the Radiotherapy Gap in Cancer Care.

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for equitable cancer care.

Analysis of Global Radiotherapy Needs and Costs by Geographic Region and Income Level.

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current needs and costs to provide full access in the different regions of the world. Actual coverage of the needs ranges from 34% in Africa to over 92% in Europe to about double the needs in North America. In line with this, proportional additional investments and operational costs are as high as more than 200% in Africa to almost none in North America. Two world regions face substantial challenges: Africa, based on the important demands to build new capacity and subsequently to maintain operational capability; and Asia Pacific, due to its high population density, translating into large absolute needs in radiotherapy treatments and resources, and hence in associated costs. With the data highlighting a large variability of GNI/capita even within similar income levels in the various world regions, it is expected that additional investment in resources and costs may be more dependent on income level of the country than on the GNI group or the geographic region of the world.

Organochlorine pesticide levels in Clarias gariepinus from polluted freshwater impoundments in South Africa and associated human health risks.

There are increasing concerns regarding the safe human consumption of fish from polluted, freshwater impoundments. The aim of this study was to analyse the muscle tissue of the sharptooth catfish Clarias gariepinus for selected organo-chlorine pesticides (OCPs) and to perform a human health risk assessment using a standard protocol described by the United States Environmental Protection Agency (US EPA). Fish were collected from the polluted Roodeplaat-(RDPD), Rietvlei-(RVD) and Hartbeespoort (HBPD) Dam impoundments located in the north-eastern regions of South Africa. GC-MS analyses showed levels of various OCPs in fish muscle samples from all three impoundments. For fish collected from the RDPD, p,p'-DDE, endosulfan, lindane and ß- and δ-HCH were the most prevalent OCPs detected, while p,p'-DDE and endosulfan were the most predominant in fish from the RVD. Lindane and ß- and δ-HCH were the main OCPs detected in fish from the HBPD. Dieldrin was the only OCP detected at concentrations for which a cancer risk and a hazard index above the acceptable risk levels were estimated. This was the case for fish from both the RDPD and RVD impoundments. No toxic risk was estimated should fish from the HBPD be consumed.

The effect of mixtures of organophosphate and carbamate pesticides on acetylcholinesterase and application of chemometrics to identify pesticides in mixtures.

Organophosphate (OP) and carbamate (CP) pesticides act by the inhibition of acetylcholinesterase (AChE). This enables the use of this enzyme for the detection of these pesticides in the environment. While many studies have looked at the effect of single pesticides on AChE, the effect of mixtures of pesticides still requires extensive investigation. This is important to evaluate the cumulative risk in the case of simultaneous exposure to multiple pesticides. Therefore we examined the effect of five different pesticides (carbaryl, carbofuran, parathion, demeton-S-methyl, and aldicarb) on AChE activity to determine whether combinations had an additive, synergistic, or antagonistic inhibitory effect. Results indicated that the mixtures had an additive inhibitory effect on AChE activity. The data from the assays of the mixtures were used to develop and train an artificial neural network (ANN) which was then utilised successfully for the identification of pesticides and their concentrations in mixtures. This study is significant because it evaluated mixtures of OPs and CPs where previous studies focused on either OPs or CPs. Previous studies have only examined up to three pesticides while this study evaluated mixtures of five pesticides simultaneously. This is also the first study where an ANN was able to utilise data from the inhibition of a single enzyme to differentiate five different pesticides and their concentrations from mixtures.

Characterization of Xyn30A and Axh43A of Bacillus licheniformis SVD1 identified by its genomic analysis.

The genome sequence of Bacillus licheniformis SVD1, that produces a cellulolytic and hemi-cellulolytic multienzyme complex, was partially determined, indicating that the glycoside hydrolase system of this strain is highly similar to that of B. licheniformis ATCC14580. All of the fifty-six genes encoding glycoside hydrolases identified in B. licheniformis ATCC14580 were conserved in strain SVD1. In addition, two new genes, xyn30A and axh43A, were identified in the B. licheniformis SVD1 genome. The xyn30A gene was highly similar to Bacillus subtilis subsp. subtilis 168 xynC encoding for a glucuronoarabinoxylan endo-1,4-ß-xylanase. Xyn30A, produced by a recombinant Escherichia coli, had high activity toward 4-O-methyl-D-glucurono-D-xylan but showed definite activity toward oat-spelt xylan and unsubstituted xylooligosaccharides. Recombinant Axh43A, consisting of a family-43 catalytic module of the glycoside hydrolases and a family-6 carbohydrate-binding module (CBM), was an arabinoxylan arabinofuranohydrolase (α-L-arabinofuranosidase) classified as AXH-m23 and capable of releasing arabinosyl residues, which are linked to the C-2 or C-3 position of singly substituted xylose residues in arabinoxylan or arabinoxylan oligomers. The isolated CBM polypeptide had an affinity for soluble and insoluble xylans and removal of the CBM from Axh43A abolished the catalytic activity of the enzyme, indicating that the CBM plays an essential role in hydrolysis of arabinoxylan.

Sci-Fri PM: Delivery - 11: Accuracy considerations in modern radiation oncology: An update.

The most recent reviews of accuracy requirements in radiation oncology were published in the 1990s, primarily in an era that was transitioning from 2-D to 3-D conformal radiation therapy (CRT). Since then, the technology associated with radiation oncology has changed dramatically. The combination of various forms of imaging for radiation therapy planning, treatment planning software, dose delivery technology including 4-D considerations as well as in-room daily image guidance has resulted in new perspectives on accuracy considerations. The underlying hypothesis for the use of these advanced technologies is that loco-regional control of cancer remains a significant barrier to cancer cure for many common cancers and that better dose distributions will translate into better outcomes. However, further clinical gain using these new technologies may be limited by single or compounded uncertainties associated with the entire treatment process. Thus, it is important to understand what factors should be considered in determining accuracy requirements as well as the realistic expectations of uncertainties that exist within the total treatment process. The need for accuracy is based on clinical requirements such as the steepness of dose-response curves, inherent heterogeneity in patient response to treatment, and the level of accuracy that is practically achievable. Statements on accuracy are dependent on the technology used and the reality of what is practically achievable and necessary. This review highlights some of the major differences between accuracy requirements as determined in the 2-D RT and 3-D CRT era versus the modern era of intensity modulated, image-guided, 4-D radiation therapy.

MO-D-BRB-01: Accuracy Requirements and Uncertainties in Radiation Therapy: A Preview of an Upcoming IAEA Report.

PURPOSE: The International Atomic Energy Agency (IAEA) has a mandate 'to accelerate and enlarge the contribution of atomic energy to peace, health and prosperity throughout the world'. Through its Human Health Division, this is done by developing guidance documents on standards of practice in radiation medicine. In recent years, there have been major advances in the technology of radiation oncology which have allowed for a transition from conventional 2-D radiation therapy to the implementation of 3-D conformal radiation therapy (CRT), intensity modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), adaptive radiation therapy (ART), and 4-D imaging and motion management in radiation therapy. Brachytherapy procedures have also evolved both for high dose rate (HDR) techniques as well as permanent implants, especially for prostate cancer treatments. Multiple imaging modalities are now available for target volume and normal tissue delineation for radiation treatment planning both for external beam radiation therapy and brachytherapy. With these new advanced technologies and improved outcome considerations for both external beam and brachytherapy, there is also a recognized need for greater accuracy in the radiation treatment process. METHODS: While a number of reports and publications have defined accuracy needs in radiation oncology, most of these reports were developed in an era with different radiation technologies and date back to the 1980s and 90s. RESULTS: In view of the new technologies and techniques, improvements in dosimetry methodologies and new clinical dose- volume data, the IAEA is developing a new international guidance document on 'Accuracy Requirements and Uncertainties in Radiation Therapy' in order to reduce these uncertainties to provide more effective and safer patient treatments. CONCLUSIONS: This review will summarize the new IAEA report which is expected to be published later in 2012. This work is supported by the International Atomic Energy Agency.

Liver histopathology of the sharptooth catfish Clarias gariepinus as a biomarker of aquatic pollution.

This paper reports on a comparative perspective of liver histopathological data of the sharptooth catfish Clarias gariepinus. The data was collected from a spectrum of relatively un-impacted and isolated, to polluted, eutrophic freshwater ecosystems. Results were compared between regional areas, by combining data from freshwater systems which has a similar pollution status and/or is located within the same geographical region. Measurements included necropsy observations, semi-quantitative liver histopathology (Liver Index), and selected biometrical indices. The aim was to establish whether the results of these measurements would differ between, and/or reflect the pollution status of, the different freshwater aquatic ecosystems. The histopathological analysis showed a higher prevalence of toxicopathic non-neoplastic, and pre-neoplastic alterations in C. gariepinus from the polluted sites. We also found a significant difference between the Liver Index, hepatosomatic index, and condition factor values of fish inhabiting impoundments known to be polluted, compared to the same species from the selected reference sites. Fish from polluted sites also had more macroscopic liver abnormalities. The results suggest that the liver histopathology of this bio-indicator fish species could be a useful biomarker of freshwater aquatic pollution.

Review on the use of enzymes for the detection of organochlorine, organophosphate and carbamate pesticides in the environment.

Pesticides are released intentionally into the environment and, through various processes, contaminate the environment. Three of the main classes of pesticides that pose a serious problem are organochlorines, organophosphates and carbamates. While pesticides are associated with many health effects, there is a lack of monitoring data on these contaminants. Traditional chromatographic methods are effective for the analysis of pesticides in the environment, but have limitations and prevent adequate monitoring. Enzymatic methods have been promoted for many years as an alternative method of detection of these pesticides. The main enzymes that have been utilised in this regard have been acetylcholinesterase, butyrylcholinesterase, alkaline phosphatase, organophosphorus hydrolase and tyrosinase. The enzymatic methods are based on the activation or inhibition of the enzyme by a pesticide which is proportional to the concentration of the pesticide. Research on enzymatic methods of detection, as well as some of the problems and challenges associated with these methods, is extensively discussed in this review. These methods can serve as a tool for screening large samples which can be followed up with the more traditional chromatographic methods of analysis.

Evaluation of megavoltage CT imaging protocols in patients with lung cancer.

Currently, megavoltage CT studies in most centres with tomotherapy units are performed prior to every treatment for patient set-up verification and position correction. However, daily imaging adds to the total treatment time, which may cause patient discomfort as well as results in increased imaging dose. In this study, four alternative megavoltage CT imaging protocols (images obtained: during the first five fractions, once per week, alternating fractions and daily on alternative weeks) were evaluated retrospectively using the daily position correction data for 42 patients with lung cancer. The additional uncertainty introduced by using a specific protocol with respect to the daily imaging, or residual uncertainty, was analysed on a patient and population bases. The impact of less frequent imaging schedules on treatment margin calculation was also analysed. Systematic deviations were reduced with increased imaging frequency, while random deviations were largely unaffected. Mean population systematic errors were small for all protocols evaluated. In the protocol showing the greatest error, the treatment margins necessary to accommodate residual errors were 1.2, 1.3 and 1.7 mm larger in the left-right, superior-inferior and anterior-posterior directions, respectively, compared with the margins calculated using the daily imaging data. The increased uncertainty because of the use of less frequent imaging protocols may be acceptable when compared with other sources of uncertainty in lung cancer cases, such as target volume delineation and motion because of respiration. Further work needs to be carried out to establish the impact of increased residual errors on dose distribution.

Schedule for CT image guidance in treating prostate cancer with helical tomotherapy.

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose distribution was performed for two patients with different patterns of interfraction changes in anatomy. Our analysis of the daily set-up correction shifts for 20 prostate cancer patients suggests that the use of four fractions would result in a population average shift that was within 1 mm of the average obtained from the data accumulated over all daily MVCT sessions. Simulation of a scenario in which imaging sessions are performed at a reduced frequency and the planning target volume margin is adapted provided significantly better sparing of organs at risk, with acceptable reproducibility of dose delivery to the clinical target volume. Our results indicate that four MVCT sessions on helical tomotherapy are sufficient to provide information for the creation of personalised target margins and the establishment of the new reference position that accounts for the systematic error. This simplified approach reduces overall treatment session time and decreases the imaging dose to the patient.

Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South Africa.

There is a need for sensitive bio-monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long-term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology-based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2.

Consistency check of planned adaptive option on helical tomotherapy.

This study aims to evaluate a new Planned Adaptive software (TomoTherapy Inc., Madison, WI) of the helical tomotherapy system by retrospective verification and adaptive re-planning of radiation treatment. Four patients with different disease sites (brain, nasal cavity, lungs, prostate) were planned in duplicate using the diagnostic planning kVCT data set and MVCT studies of the first treatment fraction with the same optimization parameters for both plan types. The dosimetric characteristics of minimum, maximum, and mean dose to the targets as well as to organs at risk were compared. Both sets of plans were used for calculation of dose distributions in a water-equivalent phantom. Corresponding measurements of these plans in phantom were carried out with the use of radiographic film and ion chamber. In the case of the lung and prostate cancer patients, changes in dosimetric parameters compared to data generated with the kVCT study alone were less than 2%. Certain changes for the nasal cavity and brain cancer patients were greater than 2%, but they were explained in part by anatomy changes that occurred during the time between kVCT and MVCT studies. The Planned Adaptive software allows for adaptive radiotherapy planning using the MVCT studies obtained by the helical tomotherapy imaging system.

[Optimization of MVCT imaging schedule in prostate cancer treatment using helical tomotherapy]. / Optimisation du processus d'imagerie de haute énergie (MVCT) pour la tomothérapie hélicoïdale des cancers de la prostate.

PURPOSE: Megavoltage CT (MVCT) study on helical tomotherapy permits to verify and correct the patient setup by coregistration with the planning kVCT. This process is time-consuming and our objective is to investigate a possibility of using a smaller number of imaging studies in the case of patients with prostate cancer. PATIENTS AND METHODS: The interfraction shifts of 20 patients (about 700 MVCT studies) treated in our institution have been recorded and analyzed. A new reference position has been calculated as an average of shifts observed during different initial number of fractions imaged. RESULTS: The analysis of the reference position obtained for the set of 20 patients as a function of the number of imaging sessions has shown that MVCT studies during first four fractions are sufficient for the majority of patients. CONCLUSION: Imaging during the first four fractions can be used to determine a reference position for patients with prostate cancer treated on helical tomotherapy. A study on Planned Adaptive (TomoTherapy Inc., Madison, WI, USA) software to evaluate the clinical significance of this scenario is currently in process in our institution.

Sci-Thurs PM: Delivery-07: Evaluation of prospects to use daily megavoltage CT studies for adaptive radiotherapy.

PURPOSE: To evaluate gross tumor volume (GTV) changes for non-small cell lung cancer (NSCLC) patients using daily megavoltage CT (MVCT) studies acquired before each treatment fraction on helical tomotherapy, and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS: 17 patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for NSCLC at London Regional Cancer Program from December 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kVCT image sets to investigate the advantages of replanning for patients with differing GTV regression characteristics. RESULTS: The average GTV change observed over 30 fractions was -38%, ranging from -12 to -87%. No significant correlation was observed between GTV change and patient's physical or tumor features. The pattern of GTV changes of the 17 patients could be broadly divided into 3 groups with distinctive potential for benefit from adaptive planning. CONCLUSIONS: GTV changes are difficult to predict quantitatively based on patient or tumor characteristics. If changes do occur, there are points in time during the treatment course when it may be appropriate to adapt the plan to improve sparing of normal tissues. If the GTV decreases by greater than 30% at any point in the first twenty fractions of treatment, adaptive planning is appropriate to further improve the therapeutic ratio.

Poster - Thurs Eve-41: Imaging and radiation delivery in helical tomotherapy: Phantom study of a moving target.

Treating lung cancer with radiation therapy by guaranteed delivery of the prescription dose to the target is difficult due to tumour motion. The standard approach to account for motion effects consists of adding a substantial margin to a lesion visible on the CT study. Larger irradiated volume results in increased dose deposition in healthy lung and the potential for patient complications. This investigation focuses on determining the optimal choice of planning CT mode for improved radiation delivery in terms of better target coverage and sparing of healthy organs. Dosimetric measurements were performed on a helical tomotherapy unit. A Quasar® (Modus Medical Devices, London, ON) respiratory phantom was imaged while a polystyrene target moved sinusoidally with a period of 4 s and amplitude of 2 cm. For target moving in superior-inferior and lateral directions, conventional fast-CT image studies were created, as well as maximum intensity projection (MIP) and average intensity projection (AveIP) image studies using four-dimensional CT information. All types of CT studies were used to develop treatment plans with a prescription of 2 Gy per fraction to the target outlined according to the imaged data. Measurements of dose deposition were made in four locations within the moving target using an Exradin A1SL ion chamber. Comparing all results to the dose measured at the centre of the static phantom, the MIP plans overdose the target, the fast-CT results vary from case to case, while the AveIP plans provide consistent dose distribution across the target within 2% of the normalization dose.