Strategic planning in an academic radiation medicine program.

BACKGROUND: In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp) at the Princess Margaret Cancer Centre. The rmp conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. METHODS: Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. RESULTS: The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. CONCLUSIONS: The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations.

Treatment planning and delivery evaluation of volumetric modulated arc therapy for stereotactic body radiotherapy of spinal tumours: impact of arc discretization in planning system.

The purpose of this study was to compare single arc volumetric modulated arc therapy (VMAT) to intensity modulated radiotherapy (IMRT) for spine SBRT in terms of target coverage, organ at risk (OAR) sparing and delivery performance. VMAT plans with 91 control points (VMAT-91CP) were generated for 15 spine metastases patients previously treated with a nine-field IMRT technique. VMAT and IMRT plans were compared based on target coverage, maximum spinal cord dose, maximum plan dose and volume of normal tissue receiving 20% to 80% of the prescribed dose. Treatment delivery time and monitor units (MU) were measured to determine delivery efficiency. To assess the impact of arc discretization in the treatment planning system (TPS), the VMAT-91CP plans were modified by almost doubling the number of CPs (VMAT-181CP). Planned-to-delivered dose agreement for both techniques was assessed using two types of 3D detector arrays.VMAT-91CP target coverage was equivalent to IMRT while maintaining or improving spinal cord sparing. This was achieved without increasing the volume of normal tissue receiving low or intermediate dose levels. Planned-to-delivered dose agreement equivalent to IMRT was achieved with VMAT, but required decreasing the CP angular spacing from 4° to 2° (VMAT-181CP plans). On average, VMAT-181CP plans reduced delivery time by 53% compared to IMRT. Single-arc VMAT for spine SBRT improved delivery efficiency while maintaining target coverage and OAR sparing compared to IMRT. VMAT plans generated with a CP gantry angular spacing of 2° is recommended to avoid a discretization effect in the TPS and ensure acceptable planned-to-delivered dose agreement.

The Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy.

AIMS: The Canadian Association of Radiation Oncology-Stereotactic Body Radiotherapy (CARO-SBRT) Task Force was established in 2010. The aim was to define the scope of practice guidelines for the profession to ensure safe practice specific for the most common sites of lung, liver and spine SBRT. MATERIALS AND METHODS: A group of Canadian SBRT experts were charged by our national radiation oncology organisation (CARO) to define the basic principles and technologies for SBRT practice, to propose the minimum technological requirements for safe practice with a focus on simulation and image guidance and to outline procedural considerations for radiation oncology departments to consider when establishing an SBRT programme. RESULTS: We recognised that SBRT should be considered as a specific programme within a radiation department, and we provide a definition of SBRT according to a Canadian consensus. We outlined the basic requirements for safe simulation as they pertain to spine, lung and liver tumours, and the fundamentals of image guidance. The roles of the radiation oncologist, medical physicist and dosimetrist have been detailed such that we strongly recommend the development of SBRT-specific teams. Quality assurance is a key programmatic aspect for safe SBRT practice, and we outline the basic principles of appropriate quality assurance specific to SBRT. CONCLUSION: This CARO scope of practice guideline for SBRT is specific to liver, lung and spine tumours. The task force recommendations are designed to assist departments in establishing safe and robust SBRT programmes.

SU-E-T-94: Multileaf Collimator Performance and Validation of Quality Control Tolerances.

PURPOSE: The automated quality assurance system (AQUA) is a centralized quality control (QC) software designed to automate QC tests. Statistical analysis of AQUA results was performed to assess the geometric accuracy and long-term reproducibility of a commercially available multileaf collimator (MLC) and examine the applicability of the American Association of Physicists in Medicine (AAPM) tolerances for MLC QC. METHODS: The MLC was first calibrated with AQUA by minimizing leaf-positioning errors on megavoltage images for 5 different leaf-bank positions (-60 to 100 mm from radiation isocenter). Leaf-positioning accuracy and reproducibility was assessed by repeating the AQUA test 5 times/week. The range of leaf-positioning error over leaf-bank positions and time was reported. Measured leaf-positioning errors were then separated into systematic and random error components. The systematic error corresponds to the variation (standard deviation) in mean positioning errors between leaves over leaf-bank positions and time. The random error quantifies the leaf position variations around its mean and is calculated as the root-mean-square of the individual leaf position standard deviations. RESULTS: To date, 2 different MLCs have been calibrated using AQUA and 9-18 datasets have been acquired to assess performance. For the unit with the longest follow up, the range of leaf-positioning errors was -0.62 to 0.85 mm and 98% of the measured leaf positions (n=7200) were within ±0.5 mm of the nominal position. The systematic error was the main error component (±0.15 to ±0.2 mm) and was attributed to the residual errors after calibration. The random error was ±0.07 mm for both units and demonstrated good leaf-positioning reproducibility and limited uncertainty of the AQUA measurements. CONCLUSIONS: Preliminary results show that after MLC calibration with AQUA, leaf-positioning errors on two different units are well within the AAPM-recommended ±1 mm tolerances. Additional MLC performance improvement is possible if residual errors after calibration can be reduced further as the MLC demonstrated high reproducibility. Funded in part by Elekta Inc.

Prospective comparison of clinical and computed tomography assessment in detecting uterine perforation with intracavitary brachytherapy for carcinoma of the cervix.

Brachytherapy (BT) is an essential component of radical treatment for cervix cancer. Uterine perforation is a potential complication of intrauterine applicator (tandem) insertion. Postprocedure pelvic computed tomography (CT) scans are routinely performed at this center. The objective of this study was to prospectively compare radiation oncologists' (RO) clinical impression of satisfactory tandem placement with actual tandem placement as determined from pelvic CT. Patients with cervix cancer undergoing low-dose rate BT from April 2003 to December 2005 were prospectively identified. After tandem placement, patients were brought to the radiotherapy department for pelvic imaging (plain films and CT). Prior to viewing imaging, the RO specified whether they were concerned vs not concerned about uterine perforation. The CT was then reviewed to determine actual tandem placement (perforation vs no perforation). One hundred twenty-four sequential tandem insertions were performed in 114 patients and eligible for analysis. The incidence of CT detected uterine perforation was 13.7% (17/124). Physician concern, age greater than or equal to 60, and tumor size were significant predictors of uterine perforation (P < 0.0001, P= 0.0019, and P= 0.0016, respectively). The overall sensitivity and specificity for physician concern was 52.9% and 84.1%, respectively. CT detected perforation in 8.2% (8/98) of insertions where the RO was clinically confident of correct tandem placement. Pelvic CT was a useful modality to accompany clinical assessment in identifying uterine perforation in cervix BT. As a low but potentially clinical significant number of perforations identified on CT were not suspected clinically, we recommend acquiring pelvic imaging in all patients following tandem insertion to ensure intrauterine tandem positioning.

Synergistic effects of three Piper amides on generalist and specialist herbivores.

The tropical rainforest shrub Piper cenocladum, which is normally defended against herbivores by a mutualistic ant, contains three amides that have various defensive functions. While the ants are effective primarily against specialist herbivores, we hypothesized that these secondary compounds would be effective against a wider range of insects, thus providing a broad array of defenses against herbivores. We also tested whether a mixture of amides would be more effective against herbivores than individual amides. Diets spiked with amides were offered to five herbivores: a naïve generalist caterpillar (Spodoptera frugiperda), two caterpillar species that are monophagous on P. cenocladum (Eois spp.), leaf-cutting ants (Atta cephalotes), and an omnivorous ant (Paraponera clavata). Amides had negative effects on all insects, whether they were naïve, experienced, generalized, or specialized feeders. For Spodoptera, amide mixtures caused decreased pupal weights and survivorship and increased development times. Eois pupal weights, larval mass gain, and development times were affected by additions of individual amides, but increased parasitism and lower survivorship were caused only by the amide mixture. Amide mixtures also deterred feeding by the two ant species, and crude plant extracts were strongly deterrent to P. clavata. The mixture of all three amides had the most dramatic deterrent and toxic effects across experiments, with the effects usually surpassing expected additive responses, indicating that these compounds can act synergistically against a wide array of herbivores.

Trade-offs in antiherbivore defenses in Piper cenocladum: ant mutualists versus plant secondary metabolites.

Ant-plant mutualisms may provide indirect evidence for costs of antiherbivore defenses when plants demonstrate trade-offs between allocating resources and energy into ant attractants versus chemical defenses. We tested the hypothesis that ecological trade-offs in defenses are present in Piper cenocladum. This plant possesses two distinct defenses: food bodies that attract predatory ants that destroy herbivore eggs and amides that deter herbivores. Previous studies have demonstrated that the food bodies in P. cenocladum are an effective defense because the ants deter herbivory by specialist herbivores. Amides in other Piper species have been shown to have toxic qualities, but we tested the additional hypothesis that these amides have an actual defensive function in P. cenocladum. To test for ecological trade-offs between the two putative defenses, fragments of P. cenocladum were examined for the presence of amides both when the plant was producing food bodies and when it was not producing food bodies. Plants with active ant colonies had redundant defenses, producing food bodies and high levels of amides at the same time, but we detected a trade-off in that they had significantly lower levels of amides than did plants with no ants. To test for the defensive value of P. cenocladum amides, we used an ant bioassay and we examined herbivory results from previous experiments with plants that had variable levels of amides. These tests demonstrated that amides are deterrent to omnivorous ants, leaf cutting ants, and orthopterans. In contrast, the resident Pheidole bicornis ants are effective at deterring herbivory by specialist herbivores that oviposit eggs on the plant but not at deterring herbivory by nonresident omnivores. We concluded that although both amides and food body production appear to be costly, redundancy in defenses is necessary to avoid damage by a complex suit of herbivores.

Validation of a noninvasive, real-time imaging technology using bioluminescent Escherichia coli in the neutropenic mouse thigh model of infection.

A noninvasive, real-time detection technology was validated for qualitative and quantitative antimicrobial treatment applications. The lux gene cluster of Photorhabdus luminescens was introduced into an Escherichia coli clinical isolate, EC14, on a multicopy plasmid. This bioluminescent reporter bacterium was used to study antimicrobial effects in vitro and in vivo, using the neutropenic-mouse thigh model of infection. Bioluminescence was monitored and measured in vitro and in vivo with an intensified charge-coupled device (ICCD) camera system, and these results were compared to viable-cell determinations made using conventional plate counting methods. Statistical analysis demonstrated that in the presence or absence of antimicrobial agents (ceftazidime, tetracycline, or ciprofloxacin), a strong correlation existed between bioluminescence levels and viable cell counts in vitro and in vivo. Evaluation of antimicrobial agents in vivo could be reliably performed with either method, as each was a sound indicator of therapeutic success. Dose-dependent responses could also be detected in the neutropenic-mouse thigh model by using either bioluminescence or viable-cell counts as a marker. In addition, the ICCD technology was examined for the benefits of repeatedly monitoring the same animal during treatment studies. The ability to repeatedly measure the same animals reduced variability within the treatment experiments and allowed equal or greater confidence in determining treatment efficacy. This technology could reduce the number of animals used during such studies and has applications for the evaluation of test compounds during drug discovery.

Cenocladamide, a dihydropyridone alkaloid from Piper cenocladum.

A dihydropyridone alkaloid, cenocladamide, and a derivative of piplartine, 4'-desmethylpiplartine were isolated along with piplartine from the leaves of Piper cenocladum. The structures of the new compounds were determined by spectroscopic methods and by comparison to piplartine. Concentrations of these amides in plants with and without ant mutualists, are compared.

[External contour acquisition system for radiotherapy: an original solution]. / Appareil de mesure de contours externes pour la radiothérapie: une solution originale.

A contour acquisition system has been designed in radiotherapy at the Sagamie Hospital complex (Chicoutimi, Québec) to measure the external contours of the patients who do not need a CT exam. This measuring system can produce transversal, sagittal or coronal patient contours in the treatment position. The absolute accuracy of the system is +/- 1 mm. The contours produced by this equipment can be transferred electronically or on paper to the planning system.

Trophic cascades in a complex terrestrial community.

To test for direct and indirect effects of a top predator on three lower trophic levels, we conducted two multiyear predator addition experiments in a tropical wet forest. Periodic additions of a top predator (predatory clerid beetle) to a wet forest understory shrub caused a reduction in the predatory beetle's prey (a predatory ant), increased herbivory, and reduced leaf area of the plant. These effects occurred whether beetles were added to naturally occurring shrubs or to reproductive fragments, suggesting fitness effects of top predators through three trophic levels. A correlational study showed that trophic effects of top predators also cascaded to nearby conspecifics in the forest understory. We use trends from understory plant surveys to suggest mechanisms by which these cascades could ultimately affect species diversity in the local plant community.

Miniature scintillating detector for small field radiation therapy.

In planning stereotactic radiosurgery treatments, depth dose curves, profiles, and dose rate of treatment beams are difficult to obtain with conventional detectors because of loss of lateral electronic equilibrium and volume averaging. A scintillating detector with high spatial resolution and good reliability has been developed to overcome this problem. The miniature dosimeter consists of two identical radiation-resistant 10 m long silica optical fibers, each connected to an independent silicon photodiode. A small cylindrical polystyrene scintillator (3.9 mm3) is optically glued to the detection fiber. The light seen by the photodiode connected to this fiber arises from fluorescence of the scintillator and from the Cerenkov effect produced in silica. The reference signal produced by the fiber without scintillator is used to subtract the Cerenkov light contribution from the raw detector response. The sensitive volume of the scintillating detector is nearly water-equivalent and thus minimizes dose distribution perturbation in water. The miniature dosimeter has a spatial resolution comparable to the film-densitometer system. Profiles of 1 cm diam, 6 MV photon beam measured with both systems show very similar shapes. Furthermore, the use of photodiodes instead of photomultiplier tubes gives a better stability response and offers the possibility to perform absolute dosimetry.

Nongestational choriocarcinoma in the postpartum period: a case report.

PURPOSE: To determine the tissue of origin (gestational versus nongestational) of an extensive metastatic choriocarcinoma in an 18-year-old woman to determine prognosis and treatment. METHODS: DNA microsatellite polymorphisms after polymerase chain reaction (PCR) amplification of the tumor tissue and blood from the patient, husband, and daughter were used to determine the tissue of origin. RESULTS: Molecular analyses revealed that the tumor shared the genetic features of only the patient. She responded well to multiagent chemotherapy. CONCLUSIONS: Molecular analysis is a useful tool to determine whether a choriocarcinoma occurring in a female patient of child-bearing age is gestational or nongestational when clinical findings are not clearly indicative of the primary.

The role of hydrophobic side chains as determinants of antibacterial activity of semisynthetic glycopeptide antibiotics.

Vancomycin, LY264826 and four N-substituted derivatives of LY264826 were examined for dimerization, binding to D-alanyl-D-alanine- and D-alanyl-D-lactate-containing cell wall ligands, and binding to bacterial membrane vesicles. The six glycopeptide antibiotics represent a 360-fold range in antibacterial activities against Micrococcus luteus (MIC = 0.00072-0.26 microM) with the N-substituted compounds having the lowest MICs. Vancomycin, LY264826 and the four N-substituted derivatives shared nearly identical binding affinities for N,N'-diacetyl-L-lysyl-D-alanyl-D-alanine (Kb = 1.5 x 10(5) approximately 5.9 x 10(5) M-1). Affinities for binding N,N'-diacetyl-L-lysyl-D-alanyl-D-lactate were lower but also represented a narrow range (Kb = 0.24 x 10(3) approximately 1.6 x 10(3) M-1). In contrast to ligand binding, the relative capacity of the six compounds to dimerize differed by four orders of magnitude (Kdim = 4.9 x 10(1)-1.2 x 10(6) M-1). The N-substituted derivatives had the highest Kdim values, required the greatest molar excess of exogenous cell wall ligand to suppress inhibition, and demonstrated a propensity to bind to bacterial membrane vesicles. The derivatives with the most lipophilic side chains were the most highly bound to vesicles. The findings suggest that the enhanced antibacterial activities of N-substituted derivatives of LY264826 derive from the nature of the hydrophobic side chain which can have a marked effect on dimerization and membrane binding.

Use of capillary electrophoresis to measure dimerization of glycopeptide antibiotics.

Capillary electrophoretic methods were used to examine dimerization and estimate dimerization constants (Kdim) for the glycopeptide antibiotics vancomycin, ristocetin A, and LY264826 (A82846B). The Kdim for LY264826 was 60- and 200-fold higher than the Kdim for ristocetin A and vancomycin, respectively. Dimerization of vancomycin measured in the presence of the cell wall analog N, N'-diacetyl-L-Lys-D-Ala-D-Ala was enhanced 200-fold; however, dimerization of ristocetin A was antagonized by the presence of N, N'-diacetyl-L-Lys-D-Ala-D-Ala. The relative differences in Kdim determined by capillary electrophoresis in general follow the same trend as those observed using nuclear magnetic resonance spectroscopy and sedimentation equilibrium.