Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

PURPOSE: To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS: Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS: While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS: When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

Concurrent platinum-based chemotherapy and hyperfractionated radiotherapy with late intensification in advanced head and neck cancer.

PURPOSE: To determine whether a course of hyperfractionated radiation therapy concomitant with escalated radiosensitizing platinum compounds can be administered with acceptable morbidity and achieve a high rate of loco-regional control for Stage III and IV head and neck cancer and whether the patients can be tumor free at the primary site after initial therapy and cured by the additional chemoradiation without radical resection of the primary tumor. METHODS AND MATERIALS: Patients with Stage III/IV head and neck cancer were treated in this multicenter Phase II Study with 1.8 Gy fraction radiotherapy for 2 weeks, with escalation to 1.2 Gy b.i.d. hyperfractionation to 46.8 Gy. Concomitant continuous infusion cisplantinum (CDDP) 20 mg per meter square on day 1 to 4 and 22 to 25 was given. Reassessment by biopsy of primary and nodes was done. Patients with a complete response continued with hyperfractionated radiotherapy to 75.6 Gy with simultaneous carboplatinum (Carbo), 25 mg per meter square b.i.d. for 12 consecutive treatment days. Patients with residual disease at 46.8 Gy required curative surgery. Seventy-four patients were treated at the three institutions; 20 were Stage III and 54 were Stage IV. All patients had daily mouth care, nutritional, and psychosocial support. RESULTS: This regime was well tolerated. Eighty-five percent of toxicities were Grade 1 or 2 and there was only one Grade 4 hematologic toxicity. Late toxicities included xerostomia in 25 patients, dysphasia in 18, and mild speech impediment in 11. Biopsies of primary site were done after the first course of treatment in 59 patients. Neck dissections were performed in 35 patients. Forty-four of 59 (75%) primary sites and 16 of 35 (46%) lymph nodes had pathologically complete response (CR). Of the 74 patients, only 12 required surgical resection of the primary site. Thirty-five of the 50 node positive patients had neck dissections, 16 of these were CRs at surgery. At 4 years (median follow-up of 26 months), disease-specific survival is 63%. The actuarial survival for all patients is 51%. Patients with pathological CR after initial treatment have disease specific survival of 73% at 4 years vs. 48% of patients with partial response (PR) only. CONCLUSION: This study, developed on the basis of radiobiological and cell kinetic precepts, produced results that compare favorably with other reports of management of patients with advanced head and neck cancer. In comparison with our previous study, these results are comparable, not impressively better. The associated morbidity was somewhat worse.

Electron contamination in 8 and 18 MV photon beams.

The contribution from contaminant electrons in the buildup region of a photon beam must be separated when calculating the dose using a photon convolution kernel. Their contribution can be extrapolated from fractional depth dose (FDD) data using the fractional depth kerma (or the "equilibrium dose") derived from measured quantities such as beam attenuation with depth, phantom scatter factor as a function of field size and depth, and inverse-square law for the incident photon beam. Good agreement is observed between the extrapolated and the EGS4 Monte Carlo simulated, primary dose-to-kerma ratios in the surface region for the photon beams, excluding electron contamination. The FDD was measured using a Scanditronix photon diode and was normalized to a reference depth far beyond maximum range of contaminant electrons. An analysis for the 8 and 18 MV photon beams from a Varian 2100CD indicates that at a source-to-surface distance (SSD) of 100 cm, the maximum electron contaminant dose (relative to its maximum FDD) varies from 1% to 33% for 8 MV and 2% to 44% for 18 MV, for square collimator settings ranging from 5 to 40 cm (defined at 100 cm from the source). This value at a depth of maximum dose (2 cm for 8 MV and 3.5 cm for 18 MV) can reach 1% for 8 MV and 2.3% for 18 MV. This contaminant electron dose is almost independent of SSD for 8 MV and starts to fall off for 18 MV at SSDs larger than 120 cm. Compared with the open beam, the contaminant electron dose increases when a solid tray is used, and the magnitude of increase increases with field size, reaching 19% and 16% for a 40 x 40 cm2 field for 8 and 18 MV photons, respectively. The contaminant electron dose increases slightly for a blocked beam compared with an open beam of the same field size if a tray is used in both cases. The contaminant electron dose for the wedged field is less than that for an open field. However, the reduction is less significant at larger collimator settings (c = 20 cm) and may increase slightly for 8 MV photons.

The head-scatter factor for small field sizes.

The head-scatter factors H were examined for four different linear accelerators and were found to be similar at field sizes larger than 3 x 3 cm2. Sharply reduced values for small collimator openings were observed for all the accelerators. It is concluded that the head-scatter (or collimator-scatter) factor has two major components. Scatter of photons in various structures in the beam path, especially the flattening filter, causes a slow (about 10%) increase with increased collimator opening. Insertion of a built-in wedge may double this number. When the collimators are closed, they ultimately block photons from the periphery of the source. This may cause a considerable reduction of the primary photon fluence and typically affects fields smaller than 3 x 3 cm2. The effect can be used to estimate the source size, with results that correlate with the design of the bending magnet.

X-ray source and the output factor.

When the collimator setting of a linear accelerator is made sufficiently small, the output factor in air, R, is greatly reduced because the collimators obstruct the periphery of the x-ray source. This has been utilized to examine the size of the source by varying the width y of a narrow field and determining how R(y) varies. The sources diameters in the two principal directions were clearly influenced by the design of the accelerators. The x-ray sources of two accelerators with bending magnets were found to be noncircular while that of a linear accelerator without a magnet showed circular symmetry. The position of the source relative to the axis of collimator rotation was determined by measuring R for offset narrow fields. For one of the accelerators, the source was initially moving and off the central axis by about 2 mm for the first five monitor units. The results correlated well with sharpness in portal-film images. The technique can serve to evaluate the major source characteristics in acceptance testing and quality control.

Characterizing output for dynamic wedges.

The output factor for the dynamic wedge, unlike that for the physical wedge, is a complex function of the field dimension along the moving jaw and wedge angle. The large change in output (varying as much as 40% for 45 degrees and 60 degrees wedge angles) can be attributed clearly to the segmented treatment tables (STTs), which specify cumulative monitor unit weighting as a function of jaw position, y. We found that the output factor (in air or water) on the central axis for the dynamic wedge can be characterized by multiplying the output factor (in air or water) for an open field by a normalization factor, which is determined from the STTs, thus indicating that collimator scatter is similar for both the dynamic wedge field and the open field. The introduction of the normalization factor decreases the commissioning time for dynamic wedges significantly and is useful for quality assurance.

Electron disequilibrium in high-energy x-ray beams.

The ratio between scatter dose and scatter kerma for points on the central axis of 15-MV x-ray beams has been examined by Monte Carlo calculations. This ratio, beta'S, behaves differently from that between the primary dose and kerma, beta'p. Both the primary and scatter components of beta' undergo an initial rapid buildup, however, beta'S begins from a much higher surface value. In addition, the depth required for longitudinal electron equilibrium is larger for beta'S than for beta'P. The variation of beta'S with field size and depth is attributed to the spatial variation of scatter kerma in the photon beam. The approximation beta'S = 1 is accurate enough for clinical dose-calculation purposes, leading to less than 0.5% error in total dose, while the assumption beta'S = beta'p may cause up to 2.5% error, relative to the maximum dose, near the surface at 15 MV.

An equivalent square field formula for determining head scatter factors of rectangular fields.

A simple formula is derived for the calculation of an equivalent square field that gives the same head scatter factor as a given rectangular field. This formula is based strictly on the configuration of a medical linear accelerator treatment head. The geometric parameters used are the distances between the target and the top of each field-defining aperture. The formula accounts for both the effect of field elongation and the collimator exchange effect. This method predicts the output to within 1% accuracy for both open and wedged fields and does not require any new measured data other than the field size dependence of head scatter for a range of square field sizes. Interestingly, the formula we derived has the same format as the formula that was empirically obtained by Vadash and Bjärngard [Med. Phys. 20, 733-734 (1993)].

A generalized solution for the calculation of in-air output factors in irregular fields.

Three major contributors of scatter radiation to the in-air output of a medical linear accelerator are the flattening filter, wedge, and tertiary collimator. These were considered separately in the development of an algorithm to be used to set up an in-air output factor calculation formalism for open and wedge fields of irregular shape. A detector's eye view (DEV) field defined at the source plane was used to account for the effects of collimator exchange and the partial blockage of the flattening filter by the tertiary collimator in the determination of head scatter. An irregular field determined at the source plane by a DEV was segmented and mapped back into the detector plane by a field-mapping method. Field mapping was performed by using a geometric conversion factor and equivalent field relationships for head scatter. The scatter contribution of each segmented equivalent field at the detector plane was summed by Clarkson integration. The same methodology was applied for determining both tertiary collimator and wedge scatter contribution. However, the field size that determined the amount of scatter contribution was not the same for each component. For tertiary collimator scatter and external wedge scatter, a field projected to the detector plane was used directly. Comparisons of calculated and measured values for in-air output factors showed good agreement for both open and external wedge fields. This algorithm can also be used for multileaf collimator (MLC) fields irrespective of the position of the MLC (i.e., whether the MLC replaces one secondary collimator or is used as a tertiary collimator). The measurement and parameterization of tertiary collimator scatter is necessary to account for its contribution to the in-air output. Because a source-plane field is mapped into the detector plane, no additional dosimetric data acquisition is necessary for the calculation of head scatter.

Tissue-phantom ratios from percentage depth doses.

When converting fractional (percentage) depth doses to tissue-phantom ratios, one must use a factor that accounts for the different source-to-point distances. Two minor correction factors are also involved. One is the ratio of total to primary dose at the two different distances from the source, for the same depth and field size. This factor is usually ignored. It was determined experimentally that this can introduce up to 1.5% error at 6 MV. The second correction factor reflects differences related to scattered photons and electrons at the depth of normalization in the two geometries. This correction is accounted for in published conversion procedures. It was found to be less than 1% provided the normalization depth is sufficient for electron equilibrium, which occurs first well beyond the depth of maximum dose. One may avoid electron-equilibrium problems by using an interim normalization depth that provides electron equilibrium with some margin, renormalizing to a shallower depth if desired. With this precaution, the accuracy when measured fractional depth doses were converted to tissue-phantom ratios was comparable to that of directly measured tissue-phantom ratios even when the correction factors were ignored.

Scattered photons from wedges in high-energy x-ray beams.

The presence of a wedge increases the fraction of "head-scattered" photons in a high-energy x-ray beam. We have compared internal and external wedges for x-ray beam energies between 6 and 25 MV by determining their SPRw, i.e., the ratio of the dose contribution from photons scattered by the wedge and photons either coming directly from the target or scattered by other structures, including the flattening filter. Marked differences were observed. First, SPRw for the thickest external wedge (60 degrees) was 1.8% at a field size of 10 x 10 cm2 and mildly dependent on the photon energy, while SPRw for internal wedges for this field size varied between 4.4% and 5.4% depending mostly on the location and size of the wedge and marginally on the photon energy. Second, the variation of SPRw with the collimator setting c x c was different for the internal and external wedges. SPRw for the internal wedge approached a limiting value at large c and could be fitted with an error function, while SPRw for the external wedge increased quadratically with c. As a result, the difference in SPRw (c) for internal and external wedges is reduced for large fields.

Photon beam skin dose analyses for different clinical setups.

A comprehensive set of data on skin dose for 8 MV and 18 MV photon beams from a medical linear accelerator was measured using a parallel-plate chamber to document the effect of field size, source-to-surface distance (SSD), off-axis distance, acrylic block tray, wedge (external standard wedge), Lipowitz's metal block, multileaf collimator (MLC), and dynamic wedge. The skin dose increased as field size increased from 5 X 5 cm2 to 40 X 40 cm2 (6% to 38% for 8 MV and 5% to 44% for 18 MV beam). With the use of an acrylic block tray, the skin dose increased for all field sizes (7% to 59% for 8 MV and 5% to 62% for 18 MV beam), but the increase was minimal for small fields. The skin dose with a wedge showed a much more complex trend. It was generally lower than the dose for an open field, but higher in the case of large fields and higher degree wedges. When both wedge and block tray were used, the tray was a major contributor to the skin dose because some of the contaminant electrons from the wedge assembly were absorbed by the block tray. Field-shaping blocks increased the skin dose, but, interestingly, the block tray reduced the skin dose for small blocked fields treated with a high-energy photon beam. The effect of an MLC on skin dose was very similar to that of a Lipowitz's metal block, but its magnitude was less. The skin dose was higher for dynamic wedge fields than it was for standard wedge fields. As SSD decreased, the skin dose increased, and this effect was dominant in larger field sizes. The SSD effect was enhanced in the presence of an acrylic block tray. The skin dose off-axis was the same as at the central axis, or smaller. A similar pattern of behavior of the skin dose is expected for photon beams from other linear accelerators.

Characteristics of bremsstrahlung in electron beams.

Clinical electron beams contain an admixture of bremsstrahlung produced in structures in the accelerator head, in field-defining cerrobend or lead cutouts, and in the irradiated patient or water phantom. Accurate knowledge of these components is important for dose calculations and treatment planning. In this study, the bremsstrahlung components are separated for electron beams (energy 6-22 MeV, diameter 0-5 cm) using measurements in water and calculations. The results show that bremsstrahlung from the accelerator head dominates and increases with field size for electron beams generated by accelerators equipped with scattering foils. The bremsstrahlung from the field-defining cerrobend accounts for 10% to 30% of the total bremsstrahlung and decreases with increasing beam radius. The bremsstrahlung is softer than the x-ray beams of corresponding nominal energy since the latter are hardened by the flattening filter. For the 6, 12, and 22 MeV electron beams, the effective attenuation coefficients in water for the bremsstrahlung are 0.058, 0.050, and 0.043 cm(-1). The depths of maximum dose at 100 cm SSD are 0.8, 1.7, and 3.0 cm. The position of the virtual source of the bremsstrahlung shifts downstream from the nominal source position by 20, 13, 5.6 cm, respectively. The lateral bremsstrahlung dose distribution is more forward-peaked for higher electron energy. The bremsstrahlung components could be described for any machine by a set of simple measurements and can be modeled by an analytical expression.

Experimental determination of the dose kernel in high-energy x-ray beams.

A semiempirical method to characterize the pencil-beam dose kernel is presented. Results from measurements are described by mathematical models of the applicable physical processes. The measurements were made with 6 and 25 MV x-ray beams from a linear accelerator. Broad-beam notations were used consistently, and the pencil-beam quantities were obtained by differentiation. The results were compared to pencil-beam kernels calculated by Monte Carlo techniques. The analysis of the measured data included a number of approximations. It was assumed that all the constituent pencil beams in the field are parallel, i.e., the divergence is ignored. Furthermore, the lateral variations of the incident photon fluence and the energy spectrum were disregarded. Monte Carlo calculations, on the other hand, are based on an average energy spectrum over the field, and are free from divergence and variations in the incident photon fluence. Measured and Monte Carlo calculated pencil beams nevertheless agreed well, and the approximations mentioned caused at maximum 2.7% discrepancies for the largest field size at 6 MV.

Modeling the output ratio in air for megavoltage photon beams.

The output ratio in air, OR, for a high-energy x-ray beam describes how the incident central axis photon fluence varies with collimator setting. For field sizes larger than 3 x 3 cm2, its variation is caused by the scatter of photons in structures in the accelerator head (primarily the flattening filter and the wedge, if one is used) and by the backscatter of radiation into the monitor ionization chamber. The objective of this study was to evaluate the use of an analytical function to parametrize OR for square collimator setting c: OR = (1 + a1.c).[1 + a2.erf(c/lambda)2].H0. For open beams, these parameters can be attributed to explicit physical meanings within the systematical uncertainty of the model: a1 accounts for backscatter into the monitor, a2 is the maximum scatter-to-primary ratio for head-scattered photons, and lambda represents the effective width of the "source" of head-scatter photons. H0 is a constant that sets OR = 1 for c = 10 cm. This formula also fits OR for wedge beams and a Co-60 unit, although the fitting parameters lose their physical interpretations. To calculate the output ratio for a rectangular field, cx x cy, an equivalent square can be used: c = (1 + k).cy x cx/(k.cx + cy), where k is a constant. The study included a number of different accelerators and a cobalt-60 unit. The fits for square fields agreed with measurements with a standard deviation (SD) of less than 0.5%. Using k = lx.(f - ly)/ly.(f - lx), where lx and ly are the source-to-collimator distances and f is the source-to-detector distance, measurements and calculations agreed within a SD of 0.7% for rectangular fields. Sufficient data for the three parameters are presented to suggest constraints that can be used for quality assurance of the measured output ratio in air.

Performance evaluation of a diode array for enhanced dynamic wedge dosimetry.

The performance of a diode array (Profiler) was evaluated by comparing its enhanced dynamic wedge (EDW) profiles measured at various depths with point measurements using a 0.03 cm3 ionization chamber on a commercial linear accelerator. The Profiler, which covers a 22.5 cm width, was used to measure larger field widths by concatenating three data sets into a larger field. An innovative wide-field calibration technique developed by the manufacturer of the device was used to calibrate the individual diode sensitivity, which can vary by more than 10%. Profiles of EDW measured with this device at several depths were used to construct isodose curves using the percentage depth dose curve measured by the ionization chamber. These isodose curves were used to check those generated by a commercial treatment planning system. The profiles measured with the diode array for both 8 and 18 MV photon beams agreed with those of the ionization chamber within a standard deviation of 0.4% in the field (defined as 80% of the field width) and within a maximum shift of less than 2 mm in the penumbra region. The percentage depth dose generally agreed to within 2% except in the buildup region. The Profiler was extremely useful as a quality assurance tool for EDW and as a dosimetry measurement device with tremendous savings in data acquisition time.

The fraction of photons undergoing head scatter in x-ray beams.

The output factor in air for a high-energy x-ray beam varies with the collimator setting. Collimator backscatter and obscuring of the source in the target contribute to this variation, but the main component is photon scatter in structures in the accelerator head. To determine the scatter-to-primary ratio, SPR, between the air kerma from such scattered photons and from those that originate directly from the source, it is essential to know the shape of this function SPR(c) of the square collimator opening c, especially for small c. To determine this, simulated head scatter was generated in lead blocks inside the head. By taking the ratio of the output factors for two such blocks of slightly different thickness, the effects of source obscuring and collimator backscatter were eliminated. Using the measured difference in transmission through the two lead blocks, the limiting value for c-->0 could be determined and hence the scatter-to-primary ratios SPR(c). The results could be fitted well with an error function, which then was applied to data measured for clinical beams of 6 and 25 MV. For c = 20 cm, SPR for one 6 MV beam was determined to be 0.016 without a flattening filter, 0.06 for the open beam, and 0.16 with the built-in wedge. At 25 MV, the SPR was higher, 0.09 and 0.20 for the open and wedged beams, respectively.

The equivalent square concept for the head scatter factor based on scatter from flattening filter.

The equivalent field relationship between square and circular fields for the head scatter factor was evaluated at the source plane. The method was based on integrating the head scatter parameter for projected shaped fields in the source plane and finding a field that produced the same ratio of head scatter to primary dose on the central axis. A value of sigma/R approximately equal to 0.9 was obtained, where sigma was one-half of the side length of the equivalent square and R was the radius of the circular field. The assumptions were that the equivalent field relationship for head scatter depends primarily on the characteristics of scatter from the flattening filter, and that the differential scatter-to-primary ratio of scatter from the flattening filter decreases linearly with the radius, within the physical radius of the flattening filter. Lam and co-workers showed empirically that the area-to-perimeter ratio formula, when applied to an equivalent square formula at the flattening filter plane, gave an accurate prediction of the head scatter factor. We have analytically investigated the validity of the area-to-perimeter ratio formula. Our results support the fact that the area-to-perimeter ratio formula can also be used as the equivalent field formula for head scatter at the source plane. The equivalent field relationships for wedge and tertiary collimator scatter were also evaluated.

Detection of epidermal cellular DNA content and its clinical significance in psoriasis vulgaris.

Epidermal cellular DNA content was detected by flow cytometry on 14 samples of normal skin and both lesional and nonlesional areas of 36 patients with psoriasis vulgaris. The results showed that the proliferative activity of epidermal cells increased in nonlesions and even more in lesions of patients from the levels in normal skin. These differences were significant (p < 0.05). Clinical features and histopathological changes were observed, and self comparisons of 6 patients before and after treatment were also done. The clinical significance of these changes was discussed.

Commissioning of enhanced dynamic wedge on a ROCS RTP system.

The enhanced dynamic wedge (EDW) is clinically commissioned on a ROCS RTPS (Version 5.03) in a manner similar to that used for any standard physical wedge. The required data set for implementation includes central axis depth dose, and open and wedge beam profiles at several depths and output factors. The features distinguishing the EDW from the physical wedge are a sharp change in output with field size in the wedge plane and a primary intensity difference at the end of the wedge field because the moving jaw stops 0.5 cm short of the fixed jaw position for all field sizes, for safety reasons. The monitor unit (MU) calculation for an EDW field in ROCS is based on scaling factors that are derived from a normalized golden STT (NGSTT). This approach requires no change in the data file structure of ROCS. It was found that the output for EDW is very sensitive to the value of final moving jaw position. Every 0.5 cm difference between planned and set value can cause 3.5% error.