A. Minken

Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer.

PURPOSE To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC). METHODS A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed. RESULTS The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% +/- 0.18% (95% CI). CONCLUSION A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.

A global calibration model for a-Si EPIDs used for transit dosimetry

Electronic portal imaging devices (EPIDs) are not only applied for patient setup verification and detection of organ motion but are also increasingly used for dosimetric verification. The aim of our work is to obtain accurate dose distributions from a commercially available amorphous silicon (a-Si) EPID for transit dosimetry applications. For that purpose, a global calibration model was developed, which includes a correction procedure for ghosting effects, field size dependence and energy dependence of the a-Si EPID response. In addition, the long-term stability and additional buildup material for this type of EPID were determined. Differences in EPID response due to photon energy spectrum changes have been measured for different absorber thicknesses and field sizes, yielding off-axis spectrum correction factors based on transmission measurements. Dose measurements performed with an ionization chamber in a water tank were used as reference data, and the accuracy of the dosimetric calibration model was determined for a large range of treatment conditions. Gamma values using 3% as dose-difference criterion and 3mm as distance-to-agreement criterion were used for evaluation. The field size dependence of the response could be corrected by a single kernel, fulfilling the gamma evaluation criteria in case of virtual wedges and intensity modulated radiation therapy fields. Differences in energy spectrum response amounted up to 30%-40%, but could be reduced to less than 3% using our correction model. For different treatment fields and (in)homogeneous phantoms, transit dose distributions satisfied in almost all situations the gamma criteria. We have shown that a-Si EPIDs can be accurately calibrated for transit dosimetry purposes.

Three‐dimensional dose reconstruction of breast cancer treatment using portal imaging

In this study, we present an algorithm for three-dimensional (3-D) dose reconstruction using portal images obtained with an electronic portal imaging device (EPID). For this purpose an algorithm for 2-D dose reconstruction, which was previously developed in our institution, was adapted. The external contour of the patient was used to correct for absorption of primary photons, but the presence of inhomogeneities was not taken into account. The accuracy of the algorithm was determined by irradiating two anthropomorphic breast phantoms with 6 MV photons. The dose values derived from portal images were compared with results from 3-D dose calculations, which, in turn, were verified with data obtained with an ionization chamber and film dosimetry. It was found that the application of contour information significantly improves the accuracy of 2-D dose reconstruction. If the total dose at the isocenter plane resulting from all treatment beams is reconstructed, the average deviation from the planned dose is 0.1%+/-1.7% (1 SD). If contour information is not available, the differences increase up to +/-20% for the individual beams. In that case, the dose can only be reconstructed with reasonable accuracy when (nearly) opposing beams are used. The average deviation of the 3-D reconstructed dose from the planned dose in the irradiated volume is 1.4%+/-5.4% (1 SD). If the irradiated volume is enclosed by planes less than 5 cm distant from the isocenter plane, then the average deviation is only 0.5%+/-3.4% (1 SD). It can be concluded that the proposed algorithm for a 3-D dose reconstruction allows a determination of the dose at the isocenter plane and the dose-volume histogram with an accuracy acceptable for an independent verification of the treatment.

A Monte Carlo based three-dimensional dose reconstruction method derived from portal dose images

The verification of intensity-modulated radiation therapy (IMRT) is necessary for adequate quality control of the treatment. Pretreatment verification may trace the possible differences between the planned dose and the actual dose delivered to the patient. To estimate the impact of differences between planned and delivered photon beams, a three-dimensional (3-D) dose verification method has been developed that reconstructs the dose inside a phantom. The pretreatment procedure is based on portal dose images measured with an electronic portal imaging device (EPID) of the separate beams, without the phantom in the beam and a 3-D dose calculation engine based on the Monte Carlo calculation. Measured gray scale portal images are converted into portal dose images. From these images the lateral scattered dose in the EPID is subtracted and the image is converted into energy fluence. Subsequently, a phase-space distribution is sampled from the energy fluence and a 3-D dose calculation in a phantom is started based on a Monte Carlo dose engine. The reconstruction model is compared to film and ionization chamber measurements for various field sizes. The reconstruction algorithm is also tested for an IMRT plan using 10 MV photons delivered to a phantom and measured using films at several depths in the phantom. Depth dose curves for both 6 and 10 MV photons are reconstructed with a maximum error generally smaller than 1% at depths larger than the buildup region, and smaller than 2% for the off-axis profiles, excluding the penumbra region. The absolute dose values are reconstructed to within 1.5% for square field sizes ranging from 5 to 20 cm width. For the IMRT plan, the dose was reconstructed and compared to the dose distribution with film using the gamma evaluation, with a 3% and 3 mm criterion. 99% of the pixels inside the irradiated field had a gamma value smaller than one. The absolute dose at the isocenter agreed to within 1% with the dose measured with an ionization chamber. It can be concluded that our new dose reconstruction algorithm is able to reconstruct the 3-D dose distribution in phantoms with a high accuracy. This result is obtained by combining portal dose images measured prior to treatment with an accurate dose calculation engine.

Experimental verification of a portal dose prediction model.

Electronic portal imaging devices (EPIDs) can be used to measure a two-dimensional (2D) dose distribution behind a patient, thus allowing dosimetric treatment verification. For this purpose we experimentally assessed the accuracy of a 2D portal dose prediction model based on pencil beam scatter kernels. A straightforward derivation of these pencil beam scatter kernels for portal dose prediction models is presented based on phantom measurements. The model is able to predict the 2D portal dose image (PDI) behind a patient, based on a PDI without the patient in the beam in combination with the radiological thickness of the patient, which requires in addition a PDI with the patient in the beam. To assess the accuracy of portal dose and radiological thickness values obtained with our model, various types of homogeneous as well as inhomogeneous phantoms were irradiated with a 6 MV photon beam. With our model we are able to predict a PDI with an accuracy better than 2% (mean difference) if the radiological thickness of the object in the beam is symmetrically situated around the isocenter. For other situations deviations up to 3% are observed for a homogeneous phantom with a radiological thickness of 17 cm and a 9 cm shift of the midplane-to-detector distance. The model can extract the radiological thickness within 7 mm (maximum difference) of the actual radiological thickness if the object is symmetrically distributed around the isocenter plane. This difference in radiological thickness is related to a primary portal dose difference of 3%. It can be concluded that our model can be used as an easy and accurate tool for the 2D verification of patient treatments by comparing predicted and measured PDIs. The model is also able to extract the primary portal dose with a high accuracy, which can be used as the input for a 3D dose reconstruction method based on back-projection.

In vivo dosimetry during conformal radiotherapy: Requirements for and findings of a routine procedure

PURPOSE Conformal radiotherapy requires accurate knowledge of the actual dose delivered to a patient. The impact of routine in vivo dosimetry, including its special requirements, clinical findings and resources, has been analysed for three conformal treatment techniques to evaluate its usefulness in daily clinical practice. MATERIALS AND METHODS Based on pilot studies, routine in vivo dosimetry quality control (QC) protocols were implemented in the clinic. Entrance and exit diode dose measurements have been performed during two treatment sessions for 378 patients having prostate, bladder and parotid gland tumours. Dose calculations were performed with a CT-based three-dimensional treatment planning system. In our QC-protocol we applied action levels of 2.5% for the prostate and bladder tumour group and 4.0% for the parotid gland patients. When the difference between the measured dose at the dose specification point and the prescribed dose exceeded the action level the deviation was investigated and the number of monitor units (MUs) adjusted. Since an accurate dose measurement was necessary, some properties of the on-line high-precision diode measurement system and the long-term change in sensitivity of the diodes were investigated in detail. RESULTS The sensitivity of all diodes decreased by approximately 7% after receiving an integrated dose of 10 kGy, for 4 and 8 MV beams. For 34 (9%) patients the difference between the measured and calculated dose was larger than the action level. Systematic errors in the use of a new software release of the monitor unit calculation program, limitations of the dose calculation algorithms, errors in the planning procedure and instability in the performance of the accelerator have been detected. CONCLUSIONS Accurate in vivo dosimetry, using a diode measurement system, is a powerful tool to trace dosimetric errors during conformal radiotherapy in the range of 2.5-10%, provided that the system is carefully calibrated. The implementation of an intensive in vivo dosimetry programme requires additional staff for measurements and evaluation. The patient measurements add only a few minutes to the total treatment time per patient and guarantee an accurate dose delivery, which is a prerequisite for conformal radiotherapy.

Verification of treatment parameter transfer by means of electronic portal dosimetry

Electronic portal imaging devices (EPIDs) are mainly used for patient setup verification during treatment but other geometric properties like block shape and leaf positions are also determined. Electronic portal dosimetry allows dosimetric treatment verification. By combining geometric and dosimetric information, the data transfer between treatment planning system (TPS) and linear accelerator can be verified which in particular is important when this transfer is not carried out electronically. We have developed a pretreatment verification procedure of geometric and dosimetric treatment parameters of a 10 MV photon beam using an EPID. Measurements were performed with a CCD camera-based iView EPID, calibrated to convert a greyscale EPID image into a two-dimensional absolute dose distribution. Central field dose calculations, independent of the TPS, are made to predict dose values at a focus-EPID distance of 157.5 cm. In the same EPID image, the presence of a wedge, its direction, and the field size defined by the collimating jaws were determined. The accuracy of the procedure was determined for open and wedged fields for various field sizes. Ionization chamber measurements were performed to determine the accuracy of the dose values measured with the EPID and calculated by the central field dose calculation. The mean difference between ionization chamber and EPID dose at the center of the fields was 0.8 +/- 1.2% (1 s.d.). Deviations larger than 2.5% were found for half fields and fields with a jaw in overtravel. The mean difference between ionization chamber results and the independent dose calculation was -0.21 +/- 0.6% (1 s.d.). For all wedged fields, the presence of the wedge was detected and the mean difference in actual and measured wedge direction was 0 +/- 3 degrees (1 s.d.). The mean field size differences in X and Y directions were 0.1 +/- 0.1 cm and 0.0 +/- 0.1 cm (1 s.d.), respectively. Pretreatment monitor unit verification is possible with high accuracy and also geometric parameters can be verified using the same EPID image.

Accurate in vivo dosimetry of a randomized trial of prostate cancer irradiation

PURPOSE To guarantee an accurate dose delivery, within +/- 2.5%, in a Phase III randomized trial of prostate cancer irradiation (68 vs. 78 Gy) by means of a comprehensive in vivo dosimetry program. METHODS AND MATERIALS Prostate patients are generally treated in our clinic with a 3-field isocentric technique: an 8-MV anteroposterior beam and 2 18-MV wedged laterals. All fields are shaped conformally to the PTV. Patients were randomized between two dose levels of 68 Gy and 78 Gy. During treatment, the entrance and exit dose were measured for each patient with diodes. Special 2.5-mm thick steel build-up caps were applied to make the diodes appropriate for measurements in 18-MV photon beams as well. Portal images were used to verify the correct position of the diodes and to detect and correct for gas filling in the rectum that may influence the exit dose reading. Entrance and exit dose measurements were converted to midplane dose, which was used in combination with a depth dose correction to obtain the dose at the specification point. An action level of 2.5% was applied. RESULTS The added build-up for the diodes in the 18-MV beams resulted in correction factors that were only slightly sensitive to changes in beam setup and comparable to the corrections used in the 8-MV beams for diodes without extra build-up. The calibration factor increased almost linearly with cumulative dose: 0.7%/kGy for the 8-MV and 1.2%/kGy for the 18-MV photon beams. The introduction of average correction factors made the analysis easier, while keeping the accuracy within acceptable limits. In a period of 3 years, 225 patients were analyzed, from which 8 patients needed to be corrected. The average ratio of measured and prescribed dose was 1.009 (standard deviation [SD] 0.012) for the total group treated on two linear accelerators. When the results were analyzed per accelerator, the ratios were 1.002 (SD, 0.001) for Accelerator A and 1.015 (SD, 0.001) for Accelerator B. This difference could be attributed to the cumulative effect of three small imperfections in the performance of Accelerator B that were well within the limits of our quality assurance program. CONCLUSION Diodes can be used for accurate in vivo dosimetry during prostate irradiation in high-energy photon beams. The dose delivery in this randomized trial is guaranteed within the 2.5% limits on an individual patient basis. This could not be achieved without the in vivo dosimetry program, despite our high-standard quality assurance program of treatment delivery.

Prediction of DVH parameter changes due to setup errors for breast cancer treatment based on 2D portal dosimetry.

Electronic portal imaging devices (EPIDs) are increasingly used for portal dosimetry applications. In our department, EPIDs are clinically used for two-dimensional (2D) transit dosimetry. Predicted and measured portal dose images are compared to detect dose delivery errors caused for instance by setup errors or organ motion. The aim of this work is to develop a model to predict dose-volume histogram (DVH) changes due to setup errors during breast cancer treatment using 2D transit dosimetry. First, correlations between DVH parameter changes and 2D gamma parameters are investigated for different simulated setup errors, which are described by a binomial logistic regression model. The model calculates the probability that a DVH parameter changes more than a specific tolerance level and uses several gamma evaluation parameters for the planning target volume (PTV) projection in the EPID plane as input. Second, the predictive model is applied to clinically measured portal images. Predicted DVH parameter changes are compared to calculated DVH parameter changes using the measured setup error resulting from a dosimetric registration procedure. Statistical accuracy is investigated by using receiver operating characteristic (ROC) curves and values for the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values. Changes in the mean PTV dose larger than 5%, and changes in V90 and V95 larger than 10% are accurately predicted based on a set of 2D gamma parameters. Most pronounced changes in the three DVH parameters are found for setup errors in the lateral-medial direction. AUC, sensitivity, specificity, and negative predictive values were between 85% and 100% while the positive predictive values were lower but still higher than 54%. Clinical predictive value is decreased due to the occurrence of patient rotations or breast deformations during treatment, but the overall reliability of the predictive model remains high. Based on our predictive model, 2D transit dosimetry measurements can now directly be translated in clinically more relevant DVH parameter changes for the PTV during conventional breast treatment. In this way, the possibility to design decision protocols based on extracted DVH changes is created instead of undertaking elaborate actions such as repeated treatment planning or 3D dose reconstruction for a large group of patients.

Cone-beam CT-based adaptive planning improves permanent prostate brachytherapy dosimetry: An analysis of 1266 patients.

Purpose To evaluate adaptive planning for permanent prostate brachytherapy and to identify the prostate regions that needed adaptation. Methods and materials After the implantation of stranded seeds, using real‐time intraoperative planning, a transrectal ultrasound (TRUS)‐scan was obtained and contoured. The positions of seeds were determined on a C‐arm cone‐beam computed tomography (CBCT)‐scan. The CBCT‐scan was registered to the TRUS‐scan using fiducial gold markers. If dose coverage on the combined image‐dataset was inadequate, an intraoperative adaptation was performed by placing remedial seeds. CBCT‐based intraoperative dosimetry was analyzed for the prostate (DSymbol, VSymbol, and VSymbol) and the urethra (DSymbol). The effects of the adaptive dosimetry procedure for Day 30 were separately assessed. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Results We analyzed 1266 patients. In 17.4% of the procedures, an adaptation was performed. Without the dose contribution of the adaptation Day 30 VSymbol would be < 95% for half of this group. On Day 0, the increase due to the adaptation was 11.8 ± 7.2% (1SD) for DSymbol and 9.0 ± 6.4% for VSymbol. On Day 30, we observed an increase in DSymbol of 12.3 ± 6.0% and in VSymbol of 4.2 ± 4.3%. For the total group, a DSymbol of 119.6 ± 9.1% and VSymbol of 97.7 ± 2.5% was achieved. Most remedial seeds were placed anteriorly near the base of the prostate. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Conclusion CBCT‐based adaptive planning enables identification of implants needing adaptation and improves prostate dose coverage. Adaptations were predominantly performed near the anterior base of the prostate.