Superficial Malignancies Research Articles

Role of Diffusion MRI and Apparent Diffusion Coefficient Measurement in the Diagnosis, Staging and Pathological Classification of Bladder Tumors

Objectives: Our aim was to investigate the role of simultaneous apparent diffusion coefficient (ADC) measurement and diffusion-weighted MRI (DWMRI) in the diagnosis and differentiation of bladder masses. Methods: Weexamined 45 patients presenting with hematuria by dynamic and diffusion MRI (at b100, b600, b1000 gradients) and cystoscopy. Thirty healthy volunteers without hematuria were also included in the study. Results from imaging techniques were compared to cystoscopic and histopathologic findings. The ADC values of benign and malignant bladder masses, and bladder tissue in healthy subjects were measured and compared with each other. Results: The mean ADC values of benign (n = 10) and malignant lesions (n = 35) were significantly lower than the mean ADC values of adjacent bladder walls and bladder walls of healthy subjects at all 3 gradients (p < 0.05). However, no significant difference was detected between benign and malignant lesions (p > 0.05). Mean ADC values of invasive tumors were significantly lower than superficial malignancies at b600 and b1000 gradients. The mean ADC values of transitional cell tumors were significantly higher than squamous cell tumors at b100 and b600 gradients. Conclusion: Simultaneous measurement ofADC and DWMRI provided useful information in the diagnosis, staging and histopathological classification of bladder tumors.

The Society for Gastrointestinal Intervention. Are We, as an Organization of Disparate Disciplines, Cooperative or Competitive?

The Society for Gastrointestinal Intervention. Are We, as an Organization of Disparate Disciplines, Cooperative or Competitive?

In vivo local fluorescence spectroscopy in PDD of superficial bladder cancer

Abstract Objective A combination of fluorescence imaging with in vivo local fluorescence spectroscopy (LFS) was used to improve the predictive ability of photodynamic diagnosis (PDD) of superficial bladder cancer after intravesical instillation of Alasense, a 5-aminolevulinic acid (5-ALA)-based agent. Material and method A total of 62 patients with superficial malignancies of the urinary bladder were included in a preliminary clinical study. Nineteen patients underwent autofluorescence (AF) examination, whereas 43 patients underwent photodynamic diagnosis (PDD) after intravesical instillation of Alasense (NIOPIK, Russia). After visual examination of the urinary bladder wall under white and blue light, fluorescence emission spectra were recorded in vivo under 442 and 532 nm laser excitation within visible red fluorescent zones that had been preliminarily revealed by fluorescence imaging. For spectral data interpretation, a spectral fluorescence parameter was introduced as a ratio of the 5-ALA-induced protoporphyrin IX-emission intensity to that of the AF emission. In the search for a quantitative criterion for this parameter, as well as a diagnostic algorithm to facilitate differentiation between inflammatory and neoplastic tissues, two approaches were tested based on: (1) a posteriori estimation of the threshold values of the spectral fluorescence parameters for inflammation and cancerous tissues, and (2) a posteriori probability of attributing an acquired emission spectrum to a histologically confirmed tissue type. Results In the group of patients without intravesical instillation of Alasense (n=19), LFS showed a dramatic drop (with a factor of 5–20, p Conclusion This preliminary clinical study shows that both approaches allow for a significant increase in the PPV of PDD of superficial bladder cancer. Therefore the combination of fluorescence imaging with in vivo LFS may be helpful for minimizing false-positive fluorescence and reducing the number of biopsies necessary.

Dosimetric verification of helical tomotherapy for total scalp irradiation

Total scalp irradiation is a treatment technique used for a variety of superficial malignancies. Helical tomotherapy is an effective technique used for total scalp irradiation. Recent published work has shown the TomoTherapy planning system to overestimate the superficial dose. In this study, the superficial doses for a helical tomotherapy total scalp irradiation have been measured on an anthropomorphic phantom using radiochromic and radiographic film as well as a new skin dosimeter, the MOSkin. The superficial dose was found to be accurately calculated by the Tomo-Therapy planning system. This is in contrast to recent reports, probably due to a combination of the smaller dose grid resolution used in planning and this particular treatment primarily consisting of beamlets tangential to the scalp. The superficial dose was found to increase from 33.6 to 41.2 Gy and 36.0 to 42.0 Gy over the first 2 mm depth in the phantom in selected regions of the PTV, measured with radiochromic film. The prescription dose was 40 Gy. The superficial dose was at the prescription dose or higher in some regions due to the bolus effect of the thermoplastic head mask and the head rest used to aid treatment setup. It is suggested that to achieve the prescription dose at the surface (< or =2 mm depth) bolus or a custom thermoplastic helmet is used.

Po-Thur Eve General-32: Evaluation of calculated total scatter factor based on predicted collimator scatter factor and phantom scatter factor for kilovoltage x-ray radiation fields

Kilovoltage x‐ray tube therapy beams are used for treatment of keloids and localized superficial malignancies. The purpose of this work is to calculate the total scatter factor for kilovoltage x‐ray radiation fields based on the predicted collimator scatter factor and the predicted phantom scatter factor. The radiation field is defined by a variable collimator with or without lead sheets on the patient's skin. Measurement and prediction have been done at tube potentials of 60, 100, 120 and 250 kVp. Our approach uses three different sets of field types: square fields defined by the collimator and square and circular fields defined by lead sheets. Two calculation methods are employed: the equivalent field method and Clarkson's method. Calculation and measurement are also done for rectangular and irregular shape fields. It is shown that while the equivalent field method may lead to errors up to about 6% for irregular fields, Clarkson's method is more accurate with errors up to 2.3%. The choice of the field type for the data base is not significant. Using the measured data for square fields defined by the collimator together with Clarkson's method is recommended. The implementation of this method requires a minimum number of measurements, which are acquired during the commissioning of the unit and can be applied in dose calculation for a variety of field shapes and sizes.

SU‐FF‐T‐366: Prediction of Collimator Scatter Factor and Phantom Scatter Factor for Kilovoltage X‐Ray Radiation Fields

Purpose: Kilovoltage x‐ray tube therapy beams are used for treatment of keloids and localized superficial malignancies. The purpose of this work is to predict the collimator scatter factor and phantom scatter factor for kilovoltage x‐ray radiation fields. Method and Materials: The radiation field is defined by a variable collimator with or without lead sheets on the patient's skin. Measurement and prediction were done at tube potentials of 60, 100, 120 and 250 kVp. Our approach uses three different sets of field types: square fields defined by the collimator and square and circular fields defined by lead sheets. Two calculation methods are employed: the equivalent field and Clarkson's method. Calculation and measurement were also done for rectangular and irregular shape fields. The relative difference between predicted and measured values is given in the form of percentage error as follows: 100% (predicted value − measured value) / (measured value). Results: The error ranges between calculated and measured collimator scatter factors for the equivalent field method and Clarkson's method are, respectively, 2.41% and 1.84%. All errors are within ±1% with Clarkson's method. The results show that Clarkson's method is more accurate at predicting collimator scatter factors. The error ranges between calculated and measured phantom scatter factors for the equivalent field method and Clarkson's method are, respectively, 6.3% and 3.5%. The spread of errors is narrower for Clarkson's method. Clarkson's method is therefore more accurate at predicting phantom scatter factors. Conclusion: Using the measured data for square fields defined by the collimator together with Clarkson's method is recommended. The implementation of this method requires a minimum number of measurements which are acquired during the commissioning of the unit and can be applied in dose calculation for a variety of field shapes and sizes.

Flattering filter design for HDR surface applicators

Purpose: Small superficial malignancies are usually treated with megavoltage electron beams on linacs. An alternative treatment of these lesions is the use of Leipzig applicators as accessories to the microSelectron-HDR system. These cup-shpaed applicators limit irradiation to the required area using tungsten-alloy shielding. A practical problem with these applicators is that the resulting isodoses are too rounded on depth, increasing dose heterogeneity laterally. The purpose of this work is to design a filter with the use of the Monte Carlo method, located at the end of the applicator, to equalize the dose laterally.

Technique for routine output verification of Leipzig applicators with a well chamber

The H-type Leipzig applicators are accessories of the microSelectron-HDR system (Nucletron, Veenendaal, The Netherlands) for treatment of superficial malignancies. Recently, the dose rate distributions in liquid water for the whole set of applicators using both source models available for the microSelectron-HDR afterloaders have been obtained by means of the experimentally validated Monte Carlo (MC) code GEANT4. Also an output table (cGy/hU) at 3 mm depth on the applicator central axis was provided. The output verification of these applicators by the user, prior to their clinical use, present practical problems: small detectors such as thermoluminescent dosimeters or parallel-plate ionization chambers are not easily used for verification in a clinical environment as they require a rigid setup with the Leipzig applicator and a phantom. In contrast, well-type ionization chambers are readily available in radiotherapy departments. This study presents a technique based on the HDR1000Plus well chamber (Standar Imaging) measurements with a special insert, which allows the output verification of the H-type Leipzig applicators on a routine basis. This technique defines correspondence factors (CF) between the in water dose rate output of the Leipzig applicators (cGy/hU) obtained with MC and the reading on the well chamber with the special insert, normalized to the HDR calibration factor with the HDR insert and to the source strength. To commission the applicators (with the well chamber and the special insert used), the physicist should check if the CF value agrees with its tabulated values presented in this work. If the differences are within 5% the tabulated output values can be used in clinical dosimetry. This technique allows the output validation of the Leipzig applicators with a well chamber widely used for HDR Ir-192 source strength measurements. It can easily be adapted to other types of well chambers for HDR source output verification.

Pharmacokinetics and clinical effects of mono‐l‐aspartyl chlorin e6 (NPe6) photodynamic therapy in adult patients with primary or secondary cancer of the skin and mucosal surfaces

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664 nm wavelength and may be useful in photodynamic therapy (PDT). This open label phase I clinical trial at the University of California, Davis Medical Center examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (basal cell carcinoma = 22 lesions, squamous cell cancer = 13 lesions, papillary carcinoma = 14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n = 4), 1.0 mg/kg (n = 3), 1.65 mg/kg (n = 3), 2.5 mg/kg (n = 3), or 3.5 mg/kg (n = 1)) 4-8 h prior to light activation. The total light dose (range 25-200 J/cm2) depended on the tumor shape and size. Light was delivered using an argon-pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28-day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed. Four weeks post-PDT, 20 of 22 basal cell carcinoma tumors (91%) showed a complete response. Eighteen of 27 other malignant cutaneous tumors showed a complete (n = 15/27, 56%) or partial (n = 3/27, 11%) response. Fewer non-responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 individual patients indicated that a two-compartment model with a residual phase best fits the data. The mean alpha, beta, and terminal half-lives were 8.63+/-2.92, 105.90+/-37.59 and 168.11+/-53.40 h (+/-1 SD), respectively. The observed mean volume of distribution was 5.94+/-2.55 l, and the mean clearance was 0.0394+/-0.0132 l/h. These values were independent of the dose administered. The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.

Superficial malignant neoplasms in southwestern Ethiopia: a cytopathological approach.

The aim of this study was to describe the distributions of superficial malignant neoplasms diagnosed by fine-needle aspiration cytology (FNAC). A prospective cross-sectional study was conducted within the Jimma Teaching Hospital, Pathology Department, Jimma University during the years between September 1998 and August 2002. Cases fulfilling cytopathological evidences of superficial malignancies were included whereas deep-seated malignancies were excluded from the study. An air-dried smear stained with the Wright staining procedure was utilized for the FNAC diagnostic technique. A total of 3,200 cases were investigated during the study period where 267 (8.3%) cases were of primary superficial malignant neoplasms, with 98 cases in the peak age group of 40-59 yr (36.7%) and a median age of 38.0 yr (range, 0.2-88 yr). The most frequent superficial cytodiagnosis was breast carcinoma, 79 (29.6%) cases; followed by non-Hodgkin's lymphomas, 37 (13.9%) cases; and soft tissue sarcomas, 26 (9.7%) cases. The overall male-to-female ratio showed preponderance to female patients (1:1.3). Carcinomas were identified more frequently in those >40 yr of age whereas sarcomas were identified in those <40 yr of age (P > 0.05). The most common malignant neoplasm in women was breast carcinomas found in 74 (27.7%) cases, whereas in men non-Hodgkin's lymphomas were found in 29 (10.9%) cases. Large proportions of carcinomas (88 cases, 33.0%), lymphomas (33 cases, 12.4%), and sarcomas (20 cases, 7.5%) were detected on the trunk, head, and neck, as well as on the lower limb regions, respectively. This study uncovered different types of superficial malignant neoplasms that are prevalent in the southwestern part of Ethiopia. The most common types of cytodiagnoses such as breast carcinomas, etc. may suggest that attention be given to future high-caliber prospective studies in trying to identify some of the associated strong risk factors for the disease under study. This study may be helpful to local health planners in prioritizing some of the commonest malignancies. Some of the diagnostic challenges of lymphomas and thyroid follicular lesions were shown also. This investigation is the first in Ethiopia and therefore may act as baseline data for similar studies in the future.

Alternative effective modality of Leipzig applicator with an electron beam for the treatment of superficial malignancies

Object: The project was designed to study the effect of the same aperture high-energy electron beams from a dual photon-energy linear accelerator with the Leipzig applicator being a successful method of treating superficial malignancy in achieving a maximum relative surface dose. Methods: Leipzig applicator with its protective cap beams and small field electron beams from a Varian Clinac 2100CD linear accelerator were used. Circular fields at 100 cm SSD were obtained from cadmium-free cerrobend shields attached to the bottom face of a 6×6 cm 2 open wall electron cone. The central axis depth–dose curves, profiles and isodose curves measurement were carried out in a water phantom (NWP, Nucletron, The Netherlands) with a pair of silicon p-type diode electron detectors (Scanditronix, Sweden) with cross-section facing the source. The output factors, central-axis depth–dose curves, 90% isodose curve depth and area, flatness at depth of maximum dose were compared and the sagittal plane leakage of the Leipzig applicator were examined. Results: The data show that the maximum dose of Leipzig applicator and all 1 cm diameters electron beam are all located at the surface. The central-axis depth–dose curve of the Ir-192 beam is attenuated in an inverse square law manner. The surface to maximum dose ratio of the electron field decreases when the aperture size increases. The specified dose depths of Leipzig applicators are at least 3–6-fold less, and the area are at least 2–5-fold less than those of same aperture electron beams. The hot spot of a Leipzig applicator is located at the top and surrounding the source for both types of applicator with a leakage dose of up to 30% of D max. Conclusions: The Leipzig applicator with 192Ir high-dose-rate brachytherapy source can be used as an alternative method to electron beam irradiation in the treatment of superficial malignancies when the bulky electron applicator is difficult to set-up and approach.

Diagnosis of Barrett's esophagus using optical coherence tomography.

OCT is a promising optical technology that permits real-time, high-resolution, cross-sectional imaging of tissue during endoscopy. It has been shown to be a highly sensitive and specific means of identifying the presence of SIM. Preliminary studies suggest that OCT is capable of grading dysplasia occurring within BE and has the potential to assist with the staging of superficial malignancies, particularly squamous cell cancers. In the near future, the capabilities of OCT systems are expected to improve with systems capable of much higher resolution and with Doppler capability becoming available.

Histological changes and involvement of apoptosis after photodynamic therapy for actinic keratoses.

Photodynamic therapy (PDT), which employs a combination of a tumour-localizing photosensitizer and visible light, has been used to treat superficial malignancies in the epidermis. To examine histological changes and the role of apoptosis in lesions of actinic keratosis (AK) after PDT using 5-aminolaevulinic acid (ALA) and excimer dye laser. After topical ALA-PDT, biopsy specimens were collected from 18 skin lesions in 15 patients with AK. Paraffin-embedded sections of the skin specimens were stained with haematoxylin and eosin. The detection of apoptosis was performed using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method, antiactivated caspase-3 antibody and anti-Fas antibody. One hour after PDT, cells with eosinophilic cytoplasm and markedly stained nuclei were found, and vacuolation of some tumour cells was noted in the lower layer of the epidermis. An infiltrate of lymphocytes and neutrophils was observed in the upper layer of the dermis. One day after PDT, all layers of the epidermis exhibited slightly degenerative necrosis, with shadow cell formation and chromatin condensation around the nuclear membrane in the lower layer of the epidermis. Necrosis in all layers of the epidermis and lymphocyte infiltration in the dermis were found 3 days after PDT. Tumour cells had disappeared and regenerative thickening of the epidermis was observed 7 days after PDT. TUNEL staining revealed apoptosis-positive cells in the epidermis in 8 of 11 specimens obtained 1 day after PDT. Activated caspase-3 expression was noted in the lower layer of the epidermis in four of these eight TUNEL-positive specimens. Results suggested that apoptosis is involved in tumour cell death after PDT in patients with AK, and that it occurs within 1 day after PDT.

Gastrointestinal cancer and sentinel node navigation surgery.

In the twentieth century, lymph node dissection based on metastatic distribution has developed as the standard procedure for surgical management of gastrointestinal cancer [1]. The fear that invisible micrometastases might be present has encouraged aggressive resection with lymphadenectomy to control the disease. However, the prognostic benefits of extensive surgery are still unknown and the universal application of radical surgery may affect surgical morbidity, mortality, and quality of life after surgery, particularly in patients without lymphatic spread. In the twenty-first century, a novel technology to detect micrometastases without extensive surgical resection is required to establish an individualized surgical management approach to gastrointestinal cancer. Lymphatic mapping techniques are now used in the control of superficial malignancies, such as malignant melanoma and breast cancer, providing a novel tool that may also be of use for gastrointestinal cancers.

Hot Topic Water-filtered infrared-A radiation: a novel technique for localized hyperthermia in combination with bacteriochlorophyll-based photodynamic therapy

A novel application of an infrared-A (IR-A) radiation source equipped with a water-filter in the radiation path is described, which allows for tumour treatment with a simultaneous combination of localized hyperthermia (HT) and bacteriochlorophyll-serine (Bchl-ser) based photodynamic therapy (PDT). Using this system, the IR-A radiation was used to heat tumours to 43 C for 60min, while at the same time activating the Bchl-ser which was injected i.v. at a dose of 20mg/ kg, 10 min following commencement of HT. The growth of tumours undergoing this combined therapy was compared to that of tumours undergoing HT alone or sham-treated controls. Within the 90 day observation period, 100% of tumours in sham-treated animals, 80% in HT-treated animals and only 17% in HT+ Bchlser-treated animals reached the end point target volume of 3.5ml. Thus, the tumour growth inhibition effect of HT can be substantially enhanced by combination with Bchl-ser-PDT. This novel technique has proved to be well-tolerated, easy to apply and should be suitable for treatment of superficial malignancies, especially where hypoxic tumour areas are present.

Clinical evaluation of 430 MHz microwave hyperthermia system with lens applicator for cancer therapy

The clinical efficacy of a microwave (MW) hyperthermia system using an electric-field converging (lens) applicator is evaluated for 42 malignant tumours with a maximum tumour depth of less than 7 cm. The mean of the maximum, average and minimum tumour temperature of the 42 tumours are 44.5, 42.5 and 40.7 C, respectively. The thermal parameters are higher for tumours in the chest, abdominal walls and hip than for those in the neck, groin and extremities. No apparent difference in thermal parameters according to the depth of tumour is shown. Of 40 tumours treated by hyperthermia in combination with radiotherapy, 20 (50%) showed complete regression, 14 (35%) showed partial regression, and six (15%) showed no change. This phase I and II study indicates clinical feasibility of the newly developed MW heating apparatus, and strongly suggests the usefulness of thermoradiotherapy in the treatment of localised superficial and subsurface malignancies.

Cumulative minutes with T 90 greater than temp index is predictive of response of superficial malignancies to hyperthermia and radiation

Purpose : To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. Methods and materials : Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0°C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24–70 Gy at 1.8–2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. Results : One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T 90) was ≥40.0°C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. Conclusions : These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer.

Photodynamic Therapy in Oncology: Mechanisms and Clinical Use

In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell death. The mechanism of cytotoxicity involves generation of singlet oxygen and other free radicals when the light-excited sensitizer loses or accepts an electron. Although selective retention of sensitizer by malignant tissue is seen in vivo, the mechanisms for this sensitizer targeting remain unclear. The first-generation sensitizers are porphyrin based and vary in lipophilicity and hydrophilicity. Targeting of the vasculature seems to be a prominent feature of the cytotoxic effect of these sensitizers in vivo, with resulting necrosis. Treatment depth varies with the wavelength of light that activates the sensitizer used, and the second-generation sensitizers are activated at longer wavelengths, allowing for a 30% increase in treatment depths. The selectivity of targeting can be increased when the sensitizer is delivered with the use of liposomes or monoclonal antibodies specific for tumor antigens. Studies have demonstrated direct effects of PDT on immune effector cells, specifically those with lineage from macrophages or other monocytes. Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors. The future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancies. Phase III trials in esophageal cancer and lung cancer are in progress and will help in evaluation of whether Photofrin II, the most widely used sensitizer, can be added to the oncologic armamentarium, pending approval from the U.S. Food and Drug Administration.

Indications, Results and Prospects of Photodynamic Therapy in the Treatment of Gastrointestinal and Genitourinary Cancers

Photodynamic therapy has been applied predominantly to patients with cutaneous and bronchial malignancies for more than a decade. More recently major interest has been focused on the endoscopic application of photodynamic therapy to tumors in hollow organs. Combining the favorable properties of laser light and a tumor localizing photosensitizer provides effective tumor destruction with a minimum of risk for the patient. Photodynamic therapy in gastrointestinal and genitourinary cancer may be indicated as an alternative to conventional therapy, particularly in superficial malignancies and localized recurrent disease.

Electron beam modifications for the treatment of superficial malignancies

For the treatment of superficial tumors, the surface dose should be high; unfortunately, because of pronounced dose buildup in low energy electron beams, their efficacy for such treatment is reduced. Electron beams can be modified by placing a low atomic number material called a beam spoiler in the beam. In general, the surface dose is a function of electron energy, source to surface distance, field size, thickness of beam spoiler, distance of beam spoiler from surface, atomic number of beam spoiler, and angle of the beam. The effects of these parameters are evaluated with respect to surface dose, bremsstrahlung dose, and field size changes for small fields at standard SSD and electron energies from 6 to 17 MeV. It was found that the use of a beam spoiler can generally increase the surface dose to values exceeding 90% of the maximum buildup value while maintaining a bremsstrahlung dose less than 3%. Changes in field size related to the placement of the beam spoiler were considerable in some cases.