Kay Willborn

BACKGROUND: Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels. METHODS: We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4). The primary end point was freedom from treatment failure; secondary end points included efficacy and toxicity of treatment. RESULTS: The two chemotherapy regimens did not differ significantly with respect to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5 years, the rates of freedom from treatment failure were 93.0% (95% confidence interval [CI], 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI, 88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy doses of radiation therapy were compared, there were also no significant differences in freedom from treatment failure (P=1.00) or overall survival (P=0.61). Adverse events and acute toxic effects of treatment were most common in the patients who received four cycles of ABVD and 30 Gy of radiation therapy (group 1). CONCLUSIONS: In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed. (Funded by the Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number, NCT00265018.)

In this paper we describe a concept for dosimetric treatment plan verification using two-dimensional ionization chamber arrays. Two different versions of the 2D-ARRAY (PTW-Freiburg, Germany) will be presented, a matrix of 16 x 16 chambers (chamber cross section 8 mm x 8 mm; the distance between chamber centers, 16 mm) and a matrix of 27 x 27 chambers (chamber cross section 5 mm x 5 mm; the distance between chamber centers is 10 mm). The two-dimensional response function of a single chamber is experimentally determined by scanning it with a slit beam. For dosimetric plan verification, the expected two-dimensional distribution of the array signals is calculated via convolution of the planned dose distribution, obtained from the treatment planning system, with the two-dimensional response function of a single chamber. By comparing the measured two-dimensional distribution of the array signals with the expected one, a distribution of deviations is obtained that can be subjected to verification criteria, such as the gamma index criterion. As an example, this verification method is discussed for one sequence of an IMRT plan. The error detection capability is demonstrated in a case study. Both versions of two-dimensional ionization chamber arrays, together with the developed treatment plan verification strategy, have been found to provide a suitable and easy-to-handle quality assurance instrument for IMRT.

The spatial resolution of 2D detector arrays equipped with ionization chambers or diodes, used for the dose verification of IMRT treatment plans, is limited by the size of the single detector and the centre-to-centre distance between the detectors. Optimization criteria with regard to these parameters have been developed by combining concepts of dosimetry and pattern analysis. The 2D-ARRAY Type 10024 (PTW-Freiburg, Germany), single-chamber cross section 5 x 5 mm(2), centre-to-centre distance between chambers in each row and column 10 mm, served as an example. Additional frames of given dose distributions can be taken by shifting the whole array parallel or perpendicular to the MLC leaves by, e.g., 5 mm. The size of the single detector is characterized by its lateral response function, a trapezoid with 5 mm top width and 9 mm base width. Therefore, values measured with the 2D array are regarded as sample values from the convolution product of the accelerator generated dose distribution and this lateral response function. Consequently, the dose verification, e.g., by means of the gamma index, is performed by comparing the measured values of the 2D array with the values of the convolution product of the treatment planning system (TPS) calculated dose distribution and the single-detector lateral response function. Sufficiently small misalignments of the measured dose distributions in comparison with the calculated ones can be detected since the lateral response function is symmetric with respect to the centre of the chamber, and the change of dose gradients due to the convolution is sufficiently small. The sampling step width of the 2D array should provide a set of sample values representative of the sampled distribution, which is achieved if the highest spatial frequency contained in this function does not exceed the 'Nyquist frequency', one half of the sampling frequency. Since the convolution products of IMRT-typical dose distributions and the single-detector lateral response function have no or very small frequency contributions beyond 0.1 mm(-1), the mathematical approach introduced by Nyquist and Shannon shows that the sampling frequency of 0.2 mm(-1) is appropriate. Overall it is shown that the spatial resolution of the 2D-ARRAY Type 10024 is appropriate for the dose verification of IMRT plans. The insights obtained are also applied in the discussion of other available two-dimensional detector arrays.

In clinical photon beams, the dose outside the geometrical field limits is produced by photons originating from (i) head leakage, (ii) scattering at the beam collimators and the flattening filter (head scatter) and (iii) scattering from the directly irradiated region of the patient or phantom (internal scatter). While the first two components can be modified, e.g. by reinforcement of shielding components or by re-modeling the filter system, internal scatter remains an unavoidable contributor to the peripheral dose. Its relative magnitude compared to the other components, its numerical variation with beam energy, field size and off-axis distance as well as its spectral distribution are evaluated in this study. We applied a detailed Monte Carlo (MC) model of our 6/15 MV Siemens Primus linear accelerator beam head, provided with ideal head leakage shielding conditions (multi-leaf collimator without gaps) to assess the head scatter contribution. Experimental values obtained under real shielding conditions were used to evaluate the head leakage contribution. It was found that the MC-computed internal scatter doses agree with the results of our previous measurements, that internal scatter is the major contributor to the peripheral dose in the near periphery while head leakage prevails in the far periphery, and that the lateral decline of the internal scatter dose can be represented by the sum of two exponentials, with an asymptotic tenth value of 18 to 19 cm. Internal scatter peripheral doses from various elementary beams are additive, so that their sum increases approximately in proportion with field size. The ratio between normalized internal scatter doses at 6 and 15 MV is approximately 2:1. The energy fluence spectra of the internal scatter component at all points of interest outside the field have peaks near 500 keV. The fact that the energy-shifted internal scatter constitutes the major contributor to the dose in the near periphery has a general bearing for dosimetry, i.e. for energy-dependent detector responses and dose conversion factors, for the relative biological effectiveness and for second primary malignancy risk estimates in the peripheral region.