Evaluation of the trade-offs encountered in planning and treating locally advanced head and neck cancer: intensity-modulated radiation therapy vs dual-arc volumetric-modulated arc therapy.

OBJECTIVE: The primary purpose of this study was to assess the practical trade-offs between intensity-modulated radiation therapy (IMRT) and dual-arc volumetric-modulated arc therapy (DA-VMAT) for locally advanced head and neck cancer (HNC). METHODS: For 15 locally advanced HNC data sets, nine-field step-and-shoot IMRT plans and two full-rotation DA-VMAT treatment plans were created in the Pinnacle(3) v. 9.0 (Philips Medical Systems, Fitchburg, WI) treatment planning environment and then delivered on a Clinac iX (Varian Medical Systems, Palo Alto, CA) to a cylindrical detector array. The treatment planning goals were organised into four groups based on their importance: (1) spinal cord, brainstem, optical structures; (2) planning target volumes; (3) parotids, mandible, larynx and brachial plexus; and (4) normal tissues. RESULTS: Compared with IMRT, DA-VMAT plans were of equal plan quality (p>0.05 for each group), able to be delivered in a shorter time (3.1 min vs 8.3 min, p<0.0001), delivered fewer monitor units (on average 28% fewer, p<0.0001) and produced similar delivery accuracy (p>0.05 at γ(2%/2mm) and γ(3%/3mm)). However, the VMAT plans took more planning time (28.9 min vs 7.7 min per cycle, p<0.0001) and required more data for a three-dimensional dose (20 times more, p<0.0001). CONCLUSIONS: Nine-field step-and-shoot IMRT and DA-VMAT are both capable of meeting the majority of planning goals for locally advanced HNC. The main trade-offs between the techniques are shorter treatment time for DA-VMAT but longer planning time and the additional resources required for implementation of a new technology. Based on this study, our clinic has incorporated DA-VMAT for locally advanced HNC. ADVANCES IN KNOWLEDGE: DA-VMAT is a suitable alternative to IMRT for locally advanced HNC.

Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

A comparative evaluation of two head and neck immobilization devices using electronic portal imaging.

A study was performed to compare the positioning reproducibility and the cost efficiency for two head and neck immobilization devices: the Uvex (Uvex Safety, Smithfield, USA) plastic mask system and the Finesse Frame with Ultraplast System (PLANET Medical, Svendborg, Denmark). 20 patients treated with 3D conformal radiation therapy for head and neck cancers were randomly selected (10 for each of the two different immobilization systems) and electronic portal images acquired during their course of treatment were saved and used in this study. The anatomical landmark coordinates and their shifts in the anteroposterior (AP) and craniocaudal (CC) directions with respect to the digitized simulator films for lateral fields were analysed using an in-house developed portal image registration system. Statistically, no evidence was found to indicate that the systematic components of the displacement for the Uvex system and the Finesse Frame with Ultraplast System were different from each other or from zero. The random component of displacement was slightly smaller in the AP direction for the Uvex than the Ultraplast system (sigma = 1.9 mm and 2.9 mm, respectively, p = 0.007), but larger in the CC direction (sigma = 3.8 mm and 2.2 mm, respectively, p<10(-9)). Production time and required materials for a radiation therapy department were also quantified to assess costs for each system. The overall costs per patient were estimated at 141.50 dollars (CAD) and 82.10 dollars for the Uvex and Ultraplast systems, respectively. The Finesse Frame with Ultraplast System of immobilization for head and neck cancer treatment provides a field placement reproducibility that is equal to, or greater than, that of the Uvex plastic mask immobilization system and, while it requires more expensive materials, the workload and consequently overall cost is greatly reduced.

The characterization of a promising new optical source for use with a radiotherapy treatment simulator.

We report on an experimental examination of a new powerful optical source with potential application in radiotherapy treatment simulation. The illuminance, effective source position, and source size have been measured for this new source and, for comparison, for conventional sources on a simulator and a linear accelerator. This new source is considerably brighter than those in common use in radiotherapy. Its effective optical source size is larger than that on the linear accelerator tested but comparable with that on a conventional simulator.

On few-view tomographic reconstruction with megavoltage photon beams.

Currently portal imaging devices are used to obtain information on patient localization during radiation therapy treatments. Such obtained information is two dimensional in nature, limited to the plane of the captured image. It has been proposed that megavoltage computed tomography images be reconstructed to overcome this limitation. This study explores the feasibility of reconstructing tomographic images from fan-beam projection data acquired with a commercial portal imaging device on a standard radiotherapy linear accelerator. Several CT reconstruction algorithms are examined as to their performance and suitability for applications in radiation therapy verification. The results show that it is possible, using some of the iterative reconstruction techniques, to obtain an image useful for patient localization from only several (< or =10) projection views.

Application of anisotropic diffusion to digital enhancement of portal images.

We propose the use of anisotropic diffusion filtering to remedy difficulties in analysis of electronic portal images, stemming from their low contrast and high noise levels. Anisotropic diffusion is a nonlinear filter based on the numerical solution to the partial differential equation describing the process of diffusion. In this study we show that this filter is capable of greatly reducing noise in homogeneous areas of portal images while preserving the edges and contrast associated with anatomical features. We also demonstrate that the application of anisotropic diffusion leads to more consistent and reproducible visual extraction of features from portal images.

Independent corroboration of monitor unit calculations performed by a 3D computerized planning system.

The checking of monitor unit calculations is recognized as a vital component of quality assurance in radiotherapy. Using straightforward but detailed computer-based verification calculations it is possible to achieve a precision of 1% when compared with a three-dimensional (3D) treatment planning system monitor unit calculation. The method is sufficiently sensitive to identify significant errors and is consistent with current recommendations on the magnitude of uncertainties in clinical dosimetry. Moreover, the approach is accurate in the sense of being highly consistent with the validated 3D treatment planning system's calculations.

Computer-assisted decision making in portal verification--optimization of the neural network approach.

PURPOSE: Conventional portal verification requires that a qualified radiation oncologist make decisions as to the set-up acceptability. This scheme is no longer sustainable with the large numbers of images available on-line and stringent time constraints. Therefore the objective of this study was to develop, optimize, and evaluate on clinical data an artificial intelligence decision-making tool for portal verification. The tool, based on the artificial neural network (ANN) approach, should approximate, as closely as possible, portal verification assessments made by a radiation oncologist expert. METHODS AND MATERIALS: A total of 328 electronic portal images of tangential breast irradiations were included in the study. A radiation oncologist expert evaluated these images and rated the treatment set-up acceptability on a scale from 0 to 10. Translational and rotational errors in the placement of the radiation field boundaries formed seven-dimensional feature vectors that represented each of the 328 portal images/treatments. The feature vectors were used as inputs to a three-layer, feedforward ANN. The neural network was trained on the oncologist's ratings. RESULTS: The rms discrepancy between the ANN and the expert's ratings was 1.05 rating points. Using the decision threshold equal to 5 for both sets of ratings, the ANN classifier was capable of detecting 100% of the portals classified as "unacceptable" by the expert. Only 6.5% of portals acceptable to the oncologist were misclassified as "unacceptable" by the ANN. CONCLUSION: The results of this study indicate the feasibility of using the ANN portal image classifier as an automated assistant to the radiation oncologist. Its role would be to recommend an appropriate decision as to the acceptability or otherwise of a given treatment set-up depicted in a portal image.

Application of a fuzzy pattern classifier to decision making in portal verification of radiotherapy.

With the large volume of electronic portal images acquired and stringent time constraints, it is no longer feasible to follow the convention whereby the radiation oncologist reviews and approves or rejects all portals. For that purpose we have developed a portal image classifier based on the fuzzy k-nearest neighbour (k-NN) algorithm. Each portal image is represented by a feature vector that consists of translational and rotational errors in the placement of radiation field borders that were measured in the portal image. Memberships in the acceptable portal class for the reference portal images within a training dataset were defined by a radiation oncologist expert. The fuzzy k-NN portal image classifier was trained and tested on a dataset of 328 portal images acquired during tangential irradiations of the breast. The memberships in the acceptable portal class produced by the fuzzy k-NN algorithm agreed very well with those defined by the expert. The linear correlation coefficient was equal to 0.89. Performance of the fuzzy k-NN classifier was also evaluated from the portal decision-making point of view using the measures of accuracy, sensitivity and specificity. The fuzzy k-NN portal classifier was capable of identifying almost all the truly unacceptable portals with an acceptably low false alarm rate.

A test tool for the visual verification of light and radiation fields using film or an electronic portal imaging device.

We describe the design and evaluation of a simple test tool which can be used in conjunction with either film or an electronic portal imaging device (EPID) to verify light and radiation fields and their congruence. The precision of the technique is better than 0.5 mm under all conditions tested. When used with film the accuracy or offset of the technique (the difference between test tool observations and a scanned conventional film) is better than 0.5 mm but, with an EPID as the image receptor, the accuracy dropped to, in one trial, 0.86 mm. The offset may be due to a systematic observer bias in determining the 50% O.D. level on the image, compounded, in the case of EPID measurements, by image acquisition and display parameters. Thus, when used with an EPID, calibration of the system will be required if absolute field dimensions are required. When used with film, the test tool method described here is of sufficient accuracy and precision to confirm the compliance of light and radiation field parameters with currently accepted quality control protocols.

Computer-aided radiation therapy simulation: image intensifier spatial distortion correction for large field of view digital fluoroscopy.

An accurate method of correcting spatial distortion in digital fluoroscopy images has been developed for generating fluoroscopy-based large field of view images for computer-aided radiation therapy simulation. This method is applicable to arbitrary gantry rotations and arbitrary shifts of the image intensifier relative to the central axis of the x-ray beam. It is therefore suitable for conventional radiation therapy simulation techniques that involve the arbitrary positioning of the image intensifier by the operator. Spatial distortion is modelled as two image intensifier orientation-dependent components, the first resulting from the projection of the x-ray image onto the curved surface of the image intensifier front end, and the second produced by the image intensifier electron optics, interactions with external magnetic fields and the video system. A geometrical model approximates the first component. The second component is modelled by a third-order polynomial transformation. A weighted mean approach is employed to achieve accurate distortion correction when the image intensifier is oriented differently from the calibration orientations. Mean and maximum residual errors (measured in the plane of the isocentre) of 0.4 mm and 1.0 mm respectively have been achieved with just 48 calibration orientations in four dimensions (gantry rotation and lateral, longitudinal and vertical shifts of the image intensifier).

An image registration scheme applied to verification of radiation therapy.

The introduction of modern conformal radiation therapy techniques requires high geometric precision in treatment delivery which must be verified. For that purpose we have developed an automated system based on registration of portal and simulation (or planning) image pairs. The image registration is performed on anatomical features which are automatically extracted from the portal image. The portal image is then registered with a planning or simulation radiographic image which represents the geometric prescription for the treatment, using an optimized version of the chamfer matching algorithm. Subsequently, the magnitude of the radiation field displacement during treatment is measured by registering the prescribed and treated field boundaries. Algorithms based on chamfer matching and polygon matching have been used for the field boundary registration. Performance of the entire scheme was evaluated on a series of 15 portal images of a pelvic phantom representing various known degrees of the radiation field displacement. The measurements of the radiation field displacements performed by the automated system proved very reliable and after correction for systematic bias agreed to within 1.5 mm or 1 degree with the displacements applied. Second test series involved comparisons between the automated registrations and those performed manually/visually by an experienced human observer, on 31 portal images acquired during treatments of 18 pelvic patients. These tests showed close agreement (in 80% of cases discrepancies were smaller than 1.5 mm or 1.5 degrees) between the automated scheme and the human observer. It is concluded that the developed scheme would be suitable for online geometric verification of radiation therapy treatments.

Urocanic acid concentration and photoisomerization in Caucasian skin phototypes.

To investigate the relationship between erythemal sensitivity of the skin to UV radiation and epidermal urocanic acid (UCA) concentration, 45 healthy volunteers of anamnestic skin phototypes (ASP) 1-IV were studied. In 16 of the subjects, we analyzed UCA photoisomerization after graded UVB exposures. The median and mean total UCA concentration in unirradiated skin was 22.4 and 35.3 nmol/cm2, and no statistically significant difference in total UCA concentrations was detectable either between ASP I through II and III through IV or between the phototested skin type (PSP) groups 1 through 2 and 3 through 4. The relative amount of the cis-isomer varied between 3 and 35%, with median and mean values of 7 and 12%, respectively. No statistically significant difference in absolute or relative cis-UCA concentrations was detectable between ASP I through II and III through IV, but a significantly lower absolute (P < 0.009) and relative (P < 0.002) cis-UCA concentration in unirradiated skin was recorded in PSP groups 1 through 2, compared to types 3 through 4. In all tested subjects, an erythemally weighted dose of 1 mJ/cm2 sufficed to cause trans- to cis-UCA isomerization. When comparing photosensitive (skin phototype I) and phototolerant (phototypes III and IV) individuals, who were irradiated with a reference 5 mJ/cm2 UV dose or with fractions of 0.1-1.0 of their individual minimal erythema dose values, no skin phototype-dependent difference in ability to photoisomerize was discernible.

The Siemens virtual wedge.

A Siemens Virtual Wedge has recently been installed and commissioned at the Northeastern Ontario Regional Cancer Centre. Measurements reported below show that 1) Virtual Wedge factors are within 1.5% of 1; 2) percentage depth doses down to 15 cm for open and virtually wedged fields are identical to within 0.7%; 3) relative cross beam profiles for 60 degrees virtual and physical wedges are very similar except at the toe end where a 5% difference in relative dose has been observed and 4) the peripheral dose from the 60 degrees Virtual Wedge is about half of that from the 60 degrees physical wedge. A clinical protocol requiring combined open and 60 degrees wedged fields has been developed and validated. This protocol, which does not impair the utility of the Virtual Wedge, facilitates the use of on-line portal imaging and significantly reduces the effort required to commission the system.

On the controversies surrounding the origins of radiation therapy.

In this study the authors analyze the documentation regarding the earliest known X-ray treatments with the objective of identifying the true origin of radiation therapy. The four most often quoted events, including X-ray treatments allegedly performed in 1896 are analyzed in the light of available published reports. From this it is concluded that Despeignes of Lyon, who in July of 1896 irradiated a patient with cancer of the stomach, is in all likelihood the first person to perform documented radiation therapy treatments with a scientific and logical basis.

The effects of the broadband UVA radiation on myeloid leukemia cells: the possible role of protein kinase C in mediation of UVA-induced effects.

We examined the effects of broadband UVA radiation (320-400 nm) on a rat myeloid leukemia cell line-chloroma (ChL). A Phillips face tanner model HB 171/A was used as a light source. Chloroma were irradiated through a 5 mm thick glass filter that cut off all of the UVB contamination. The irradiances were measured, from 250 to 400 nm, with a well-characterized and calibrated double-grating spectroradiometer Optronic 742. The overall uncertainty of dose evaluation was estimated to be +/-15% (2 sigma). The cells were irradiated with UVA doses of 4 and 8 J/cm2 and cultured thereafter for 24 h. After this period of time, a marked decline up to 50% was observed in cell proliferation in UVA-irradiated ChL cultures. The cell proliferation decline was found to be caused by simultaneously occurring G2/M phase cell cycle arrest and apoptosis in part of the UVA-irradiated ChL population. Concomitantly, with the decline in cell proliferation, an increase was observed in the expression of the major histocompatibility (MHC) class I and II antigens. Because protein kinase C (PKC) is known to regulate cell proliferation, apoptosis and expression of MHC antigens, and because UVA was shown to regulate PKC activity/expression, we therefore examined whether UVA irradiation has any effect on the expression of isozymes of PKC. Western blots revealed that ChL express alpha, beta I, delta, epsilon, eta, and zeta/iota isozymes of PKC and that expression of all isozymes declined 24 h after UVA irradiation (8 J/cm2). Finally, PKC activation in ChL by exposure to phorbol ester caused cell cycle arrest in G1 phase but did not induce apoptosis. This suggests that the previously shown UVA-induced PKC activation in ChL might be responsible for the induction of MHC antigens but the simultaneously observed ChL apoptosis is likely to be mediated by PKC down-regulation. All together, our results suggest that UVA, at irradiance levels that resemble the outdoor exposure, may have profound effects on the immune-related properties of leukocytes. Thus, we speculate that in vivo the immune functions of leukocytes passing through dermal capillaries might be altered by exposure to solar UVA radiation.

Quantitative vs. subjective portal verification using digital portal images.

PURPOSE: Off-line, computer-aided prescription (simulator) and treatment (portal) image registration using chamfer matching has been implemented on PC based viewing station. The purposes of this study were (a) to evaluate the performance of interactive anatomy and field edge extraction and subsequent registration, and (b) to compare observer's perceptions of field accuracy with measured discrepancies following anatomical registration. METHODS AND MATERIALS: Prescription-treatment image pairs for 48 different patients were examined in this study. Digital prescription images were produced with the aid of a television camera and a digital frame grabber, while the treatment images were obtained directly from an on-line portal imaging system. To facilitate perception of low contrast anatomical detail, on-line portal images were enhanced with selective adaptive histogram equalization prior to extraction of anatomical edges. Following interactive extraction of anatomical and field border information by an experienced observer, the identified anatomy was registered using chamfer matching. The degree of conformity between the prescription and treatment fields was quantified using several parameters, which included relative prescription field coverage and overcoverage, as well as the translational and rotational displacements as measured by chamfer matching applied to the boundaries of the two fields. These quantitative measures were compared with subjective evaluations made by four radiation oncologists. RESULTS: All the images in this series that included a range of the most commonly seen treatment sites were registered and the conformity parameters were found. The mean treatment/prescription field coverage and overcoverage were approximately 95 and 7%, respectively before registration. The mean translational displacement in the transverse and cranio-caudal directions were 2.9 and 3.4 mm, respectively. The mean rotational displacement was approximately 2 degrees. For all four oncologists, the portals classified as unacceptable, in terms of the field placement, exhibited significantly higher (p < 0.03) translational errors in the transverse direction. The field coverages were significantly lower (p < 0.05) and the translational errors in the cranio-caudal direction were significantly higher (p < 0.05) for the portals rated as unacceptable by two of the oncologists. CONCLUSIONS: From the parameters that were used to quantify the degree of conformity between the prescription and treatment fields, the translational error in the transverse direction correlated best with the oncologists' assessments on the field placement. Field coverage and translational error in the cranio-caudal direction correlated well with assessments of only two out of the four participating oncologists. This can be explained by the fact that for the majority of treatment sites included in the study the positioning of field borders was more critical for the transverse direction. A conclusion for the design of future quantitative and automated on-line portal verification systems is that they will have to model different perceived significances of different types of localization errors intrinsic to oncologist evaluation of portal images.

Ultraviolet erythema sensitivity in anamnestic (I-IV) and phototested (1-4) Caucasian skin phototypes: the need for a new classification system.

The anamnestic skin phototypes (ASP) I-IV of 22 Caucasian volunteers wee compared with their phototested skin phototypes (PSP) using solar simulating, broadband UV radiation. The Commission Internationale de l'Eclairage (CIE)-weighted (i.e. erythemally effective) minimal erythema doses (MED) for solar simulating radiation varied from 20 mJ/cm2 (PSP type 1) to 57 mJ/cm2 (PSP type 4). In only 11 of 21 volunteers did the ASP (I-IV) and PSP (1-4) classifications coincide, and the MED values of the volunteers within the different ASP groups (I-IV) overlapped considerably. To compare the reactivity to erythematogenic radiation of different wavelengths, narrowband monochromator irradiations were performed at 298 nm, 310 nm and 330 nm. The CIE-weighted MED values at these wavelengths (20-80 mJ/cm2) corresponded well with those obtained in the broadband testing. Our results indicate that, with classification by interrogation, Caucasian skin can reliably be classified into only two subtypes, corresponding to Fitzpatrick phototypes I-III and phototype IV, respectively. A classification into four sensitivity types can be achieved by phototesting, only. We propose that the concept of ASP should be used with caution. The concept of PSP 1-4 should be favored.

A polygon matching algorithm and its applications to verification of radiation field placement in radiotherapy.

An automated method for quantitative evaluation of geometric accuracy of radiation field placement during radiation therapy treatments has been developed and is presented in this article. The method is based on matching polygons representing the boundaries of the prescribed and treated radiation fields. An efficient algorithm for finding the intersection of two arbitrary simple polygons has been developed for that purpose. The process of polygon matching is performed by iterative optimization of the goodness-of-match measure derived from the area of the intersection between the two polygons to be matched. The optimization is done with respect to the translation and rotation in the plane that are applied to the polygon representing the treated field. The optimum translation and rotation define the adjustments in the position of the treated field, relative to the patients anatomy, which are necessary in order to bring the treated field into the best possible agreement with the prescription. The radiation field matching scheme was applied to a clinical dataset consisting of prescription-treatment field pairs extracted from simulation and portal images for 40 patients. It is concluded that the observed accuracy and efficiency of the method make it very suitable for applications in radiation therapy verification.

Increased UV exposure in Finland in 1993.

Exceptionally low total ozone, up to 40% below the normal level, was measured over Northern Europe during winter and spring in 1992 and 1993. In 1993 the depletion persisted up to the end of May, resulting in a significant increase of biologically effective UV radiation. The increases were significantly smaller in 1992 and 1993 than in 1993. The UV exposure of the Finnish population was evaluated through measurements and theoretical calculations. The increase in measured erythemal (International Lighting Commission) UV falling onto horizontal surfaces on clear day was determined relative to model calculations for an average ozone amount. The increase was on average 10% from April to May 1993, and the maximal measured increase was 34%. Theoretical calculations for both erythemal and carcinogenic (Skin Cancer Utrecht--Philadelphia) UV indicated that in 1993 the theoretical annual increase to a vertical (cylinder) surface ranged from 8 to 13% in Finland. The reflection of UV from snow considerably increases facial UV doses in Northern Finland.