Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer.

OBJECTIVE: For locally advanced cervical cancer patients, treated with External Beam Radiotherapy (EBRT), Quality of Life (QoL) questionnaires arefrequently used to evaluate treatment-related symptoms and functioning scales. Currently, it is unknown how those evolve during the radiation treatment course. In this prospective study we report on weekly-captured patient-reported QoL and symptoms during image-guided adaptive radiotherapy (IGART) of cervical cancer patients. MATERIAL AND METHODS: Between January 2012 and September 2016, all locally advanced cervical cancer patients treated with IGART and brachytherapy with or without chemotherapy or hyperthermia, were eligible. QoL was assessed at baseline; weekly during the first five weeks of treatment; 1week, 1 and 3months after treatment, using the EORTC QLQ-C30 and the QLQ-CX24 questionnaires. Comparisons were made with an age-matched norm population. RESULTS: Among the 138 (70%) responders, most symptoms showed a moderate-to-large increase, reaching a maximum at the end of treatment, or first week after treatment with return to baseline value at 3months after treatment. While most symptoms gradually increased during the first five weeks, diarrhea and bowel cramps already markedly increased within the first three weeks to reach a plateau at the 5th week of treatment. Global health and functioning were temporarily decreased and returned to a plateau at baseline level 3months after treatment, except for cognitive functioning. CONCLUSION: A profound impact on QoL was observed during the radiation treatment course, temporarily affecting functioning. The maximum impaired was reached at the end of EBRT.

SISS-MCO: large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans.

Objective.Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013).Approach.In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots.Main results.Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar.Significance.The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.

Reducing the lateral dose penumbra in IMPT by incorporating transmission pencil beams.

OBJECTIVE: In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission ('shoot through') pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams ('IMPT&TPB') could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams. APPROACH: Our system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic 'wish-list' with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams. MAIN RESULTS: Clinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D2% by up to 11.1 Gy. CONCLUSION: Compared to IMPT, IMPT&TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.

TBS-BAO: fully automated beam angle optimization for IMRT guided by a total-beam-space reference plan.

Properly selected beam angles contribute to the quality of radiotherapy treatment plans. However, the beam angle optimization (BAO) problem is difficult to solve to optimality due to its non-convex discrete nature with many local minima. In this study, we propose TBS-BAO, a novel approach for solving the BAO problem, and test it for non-coplanar robotic CyberKnife radiotherapy for prostate cancer. First, an ideal Pareto-optimal reference dose distribution is automatically generated usinga priorimulti-criterial fluence map optimization (FMO) to generate a plan that includes all candidate beams (total-beam-space, TBS). Then, this ideal dose distribution is reproduced as closely as possible in a subsequent segmentation/beam angle optimization step (SEG/BAO), while limiting the number of allowed beams to a user-selectable preset value. SEG/BAO aims at a close reproduction of the ideal dose distribution. For each of 33 prostate SBRT patients, 18 treatment plans with different pre-set numbers of allowed beams were automatically generated with the proposed TBS-BAO. For each patient, the TBS-BAO plans were then compared to a plan that was automatically generated with an alternative BAO method (Erasmus-iCycle) and to a high-quality manually generated plan. TBS-BAO was able to automatically generate plans with clinically feasible numbers of beams (∼25), with a quality highly similar to corresponding 91-beam ideal reference plans. Compared to the alternative Erasmus-iCycle BAO approach, similar plan quality was obtained for 25-beam segmented plans, while computation times were reduced from 10.7 hours to 4.8/1.5 hours, depending on the applied pencil-beam resolution in TBS-BAO. 25-beam TBS-BAO plans had similar quality as manually generated plans with on average 48 beams, while delivery times reduced from 22.3 to 18.4/18.1 min. TBS reference plans could effectively steer the discrete non-convex BAO.

Stereotactic body radiation therapy for colorectal liver metastases.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases. METHODS: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was 1 (range 1-3) and median size was 2.3 (range 0.7-6.2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis. RESULTS: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients had an episode of hepatic toxicity grade 3. CONCLUSION: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA.

Optically stimulated luminescence (OSL) of carbon-doped aluminum oxide (Al2O3:C) for film dosimetry in radiotherapy.

INTRODUCTION AND PURPOSE: Conventional x-ray films and radiochromic films have inherent challenges for high precision radiotherapy dosimetry. Here we have investigated basic characteristics of optically stimulated luminescence (OSL) of irradiated films containing carbon-doped aluminum oxide (Al2O3:C) for dosimetry in therapeutic photon and electron beams. MATERIALS AND METHODS: The OSL films consist of a polystyrene sheet, with a top layer of a mixture of single crystals of Al2O3:C, ground into a powder, and a polyester base. The total thickness of the films is 0.3 mm. Measurements have been performed in a water equivalent phantom, using 4, 6, 10, and 18 MV photon beams, and 6-22 MeV electron beams. The studies include assessment of the film response (acquired OSL signal/delivered dose) on delivered dose (linearity), dose rate (1-6 Gy/min), beam quality, field size and depth (6 MV, ranges 4 x 4-30 x 30 cm2, dmax-35 cm). Doses have been derived from ionization chamber measurements. OSL films have also been compared with conventional x-ray and GafChromic films for dosimetry outside the high dose area, with a high proportion of low dose scattered photons. In total, 787 OSL films have been irradiated. RESULTS: Overall, the OSL response for electron beams was 3.6% lower than for photon beams. Differences between the various electron beam energies were not significant. The 6 and 18 MV photon beams differed in response by 4%. No response dependencies on dose rate were observed. For the 6 MV beam, the field size and depth dependencies of the OSL response were within +/-2.5%. The observed inter-film response variation for films irradiated with the same dose varied from 1% to 3.2% (1 SD), depending on the measurement day. At a depth of 20 cm, 5 cm outside the 20 x 20 cm2 6 and 18 MV beams, an over response of 17% was observed. In contrast to GafChromic and conventional x-ray films, the response of the Al2O3:C films is linear in the clinically relevant dose range 0-200 cGy. CONCLUSIONS: Measurement of the OSL signal of irradiated films containing Al2O3:C is a promising technique for film dosimetry in radiotherapy with no or small response variations with dose rate, beam quality, field size and depth, and a linear response from 0 to 200 cGy.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

A novel approach to accurate portal dosimetry using CCD-camera based EPIDs.

A new method for portal dosimetry using CCD camera-based electronic portal imaging devices (CEPIDs) is demonstrated. Unlike previous approaches, it is not based on a priori assumptions concerning CEPID cross-talk characteristics. In this method, the nonsymmetrical and position-dependent cross-talk is determined by directly imaging a set of cross-talk kernels generated by small fields ("pencil beams") exploiting the high signal-to-noise ratio of a cooled CCD camera. Signal calibration is achieved by imaging two reference fields. Next, portal dose images (PDIs) can be derived from electronic portal dose images (EPIs), in a fast forward-calculating iterative deconvolution. To test the accuracy of these EPI-based PDIs, a comparison is made to PDIs obtained by scanning diode measurements. The method proved accurate to within 0.2+/-0.7% (1 SD), for on-axis symmetrical and asymmetrical fields with different field widths and homogeneous phantom thicknesses, off-axis Alderson thorax fields and a strongly modulated IMRT field. Hence, the proposed method allows for fast, accurate portal dosimetry. In addition, it is demonstrated that the CEPID cross-talk signal is not only induced by optical photon reflection and scatter within the CEPID structure, but also by high-energy back-scattered radiation from CEPID elements (mirror and housing) towards the fluorescent screen.

Improvement of radiotherapy treatment delivery accuracy using an electronic portal imaging device.

Reliable application of advanced external beam techniques for the treatment of patients with cancer, such as intensity modulated radiotherapy, requires an adequate quality assurance programme for the verification of the dose delivery. Accurate patient positioning is mandatory because of the steep dose gradients outside the tumour volume. Owing to the increased complexity of the treatment planning and delivery techniques, verification of the dose delivery before and during the actual patient treatment is equally important. For this purpose, a quality assurance programme has been established in our clinic that is primarily based on measurements with electronic portal imaging devices. To minimise systematic set-up errors, the patient positioning is measured in the first few treatment fractions and a set-up correction is applied in the subsequent ones. Before the first treatment fraction, portal dose measurements are performed for each treatment field with the electronic portal imaging device to verify that the planned fluence distribution is correctly delivered at the treatment unit. Dosimetric measurements are also performed during patient treatment to derive the actually delivered fluence maps. By combining this information with knowledge on the patient set-up, the delivered 3-D dose distribution to both the tumour and sensitive organs may be assessed. However, for the highest accuracy, exact knowledge on the (internal) patient geometry during treatment, e.g. using a cone-beam CT, is required.

A protocol for the reduction of systematic patient setup errors with minimal portal imaging workload.

PURPOSE: To evaluate a new off-line patient setup correction protocol that minimizes the required number of portal images and perform a comparison with currently applied protocols. METHODS AND MATERIALS: We compared two types of off-line protocols: (a) the widely applied shrinking action level (SAL) protocol, in which the setup error, averaged over the measured treatment fractions, is compared with a threshold that decreases with the number of measurements, to decide if a correction is necessary; and (b) a new "no-action-level" (NAL) protocol, which simply calculates the mean setup error over a fixed number of fractions, and always corrects for it. The performance of the protocols was evaluated by applying them to (a) a database of measured setup errors from 600 prostate patients (with, on average, 10 imaged fractions/patient) and (b) Monte Carlo-generated setup error distributions for various values of the population systematic and random errors. RESULTS: The NAL protocol achieved a significantly higher accuracy than the SAL protocol for a similar workload in terms of image acquisition and analysis, as well as in setup corrections. The SAL protocol required approximately three times more images than the NAL protocol to obtain the same reduction of systematic errors. Application of the NAL protocol to measured setup errors confirmed its efficacy in systematic error reduction in a real patient population. CONCLUSION: The NAL protocol performed much more efficiently than the SAL protocol for both actually measured and simulated setup data. The resulting decrease in required portal images not only reduces workload, but also dose to healthy tissue, if dedicated large fields are required for portal imaging (double exposure).

Transit dosimetry with an electronic portal imaging device (EPID) for 115 prostate cancer patients.

PURPOSE: Comparison of predicted portal dose images (PDIs) with PDIs measured with an electronic portal imaging device (EPID) may be used to detect errors in the dose delivery to patients. However, these comparisons cannot reveal errors in the MU calculation of a beam, since the calculated number of MU is used both for treatment (and thus affects the PDI measurement) and for PDI prediction. In this paper a method is presented that enables "in vivo" verification of the MU calculation of the treatment beams. The method is based on comparison of the intended on-axis patient dose at 5 cm depth for each treatment beam, D5, with D5 as derived from the portal dose Dp measured with an EPID. The developed method has been evaluated clinically for a group of 115 prostate cancer patients. METHODS AND MATERIALS: The patient dose D5 was derived from the portal dose measured with a fluoroscopic EPID using (i) the predicted beam transmission (i.e., the ratio of the portal dose with and without the patient in the beam) calculated with the planning CT data of the patient, and (ii) an empirical relation between portal doses Dp and patient doses D5. For each beam separately, the derived patient dose D5 was compared with the intended dose as determined from the relative dose distribution as calculated by the treatment planning system and the prescribed isocenter dose (2 Gy). For interpretation of observed deviating patient doses D5, the corresponding on-axis measured portal doses Dp were also compared with predicted portal doses. RESULTS: For three beams, a total of 7828 images were analyzed. The mean difference between the predicted patient dose and the patient dose derived from the average measured portal dose was: 0.4+/-3.4% (1 SD) for the anterior-posterior (AP) beam and -1.5+/-2.4% (1 SD) for the lateral beams. For 7 patients the difference between the predicted portal dose and the average measured portal dose for the AP beam and the corresponding difference in patient dose were both greater than 5%. All these patients had relatively large gas pockets (3-3.5 cm in AP direction) in the rectum during acquisition of the planning CT, which were not present during (most) treatments. CONCLUSIONS: An accurate method for verification of the MU calculation of an x-ray beam using EPID measurements has been developed. The method allows the discrimination of errors that are due to changes in patient anatomy related to appearance or disappearance of gas pockets in the rectum and errors due to a deviating cGy/MU-value.

Chest wall irradiation with MLC-shaped photon and electron fields.

PURPOSE: To improve the treatment technique for chest wall irradiation, using the multileaf collimator (MLC) of the MM50 Racetrack Microtron to shape both photon and electron beams, and to check the dose delivery in the match-line region of these fields for the routine and improved technique. METHODS AND MATERIALS: Using diode and film phantom measurements, the optimal number of photon beam segments and their positions relative to the electron beam were determined. On phantoms, and during actual patient treatment using in vivo dosimetry, the dose homogeneity in the match-line region was determined for both the routine and improved techniques. RESULTS: Three photon beam segments (9-mm gap, perfect match, and 9-mm overlap) were used to match the electron beam, resulting in minimum-maximum dose values in the match-line region of 88-109%, compared to 80-115% for the routine technique (2 photon beam segments). During patient treatment, the average minimum and maximum dose values were 95% and 115%, respectively, compared to 78% and 127%, respectively, for the routine technique. The interfraction variation in dose delivery was reduced from 11.0% (1 SD) to 4.6% (1 SD). The actual treatment time was reduced from 10 to 4.5 min. CONCLUSION: Using the MLC of the MM50 to shape both photon and electron beams, an improved treatment technique for chest wall irradiation was developed, which is less labor intensive, faster, and yields a more homogeneous, and better reproducible dose delivery.

Beam intensity modulation for penumbra enhancement in the treatment of lung cancer.

PURPOSE: A treatment planning study was performed for patients with lung cancer in order to investigate the extent to which doses to critical structures could be reduced by penumbra enhancement at the superior and inferior field edges, using beam intensity modulation (BIM) with a multileaf collimator. By applying two independent published models for the prediction of the incidence of normal tissue complications, the potential for dose escalation without increasing the incidence of pneumonitis was estimated. METHODS AND MATERIALS: For 12 patients, the standard treatment technique was compared with the BIM technique using the Cadplan 3D planning system (Varian-Dosetek). Dose distributions in the healthy lung tissue were evaluated by considering both lungs minus the tumor as one functional unit. The following parameters were compared: (i) the average normalized total dose (NTD), (ii) the lung volume receiving an NTD of more than 20 Gy, and (iii) the calculated normal tissue complication probability (NTCP). RESULTS: Due to the applied BIM technique, the field lengths could be reduced by 1.4 cm for all patients, while achieving a minimum dose at the superior and inferior parts of the target of 95% of the isocenter dose. Compared to the standard technique, BIM reduced the patient mean of the average NTD for the healthy lung tissue from 16.5 to 15.3 Gy. The volume of healthy lung tissue receiving an NTD of 20 Gy or more was reduced by 9.7% (range 2.2 to 23.1%). The calculated NTCP reduced from 10.7% to 7.6% on average. The length of the esophagus that received a dose of 60 Gy or more could be reduced for 5 of the 6 stage III patients in this study. Based on equal lung NTCPs for the standard technique and the BIM technique, a mean dose escalation of 5.7 Gy (range 1.1 to 16.0 Gy) was possible for the 12 patients in this study. Based on equal average NTDs for the two techniques, the patient mean of the allowed dose escalation was 6.5 Gy (range 1.1 to 18.2 Gy). All dose escalations would be possible without exceeding the spinal cord tolerance dose. CONCLUSIONS: The BIM technique reduced the dose delivery to critical tissues. Two published methods for estimating the incidence of pneumonitis both pointed to a potential for dose escalation of 6 to 7 Gy on average with the BIM technique, without increasing the incidence of pneumonitis. For 2 of the 12 patients in this study the estimated allowed dose escalation even exceeded 15 Gy.

Field margin reduction using intensity-modulated x-ray beams formed with a multileaf collimator.

PURPOSE: In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTV) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose. METHODS AND MATERIALS: The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The application of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields. RESULTS: Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for the setup and delivery of the boost fields is usually about 1 min. CONCLUSION: The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning.

PURPOSE: To determine the magnitude of the errors made in (a) the setup of patients with lung cancer on the simulator relative to their intended setup with respect to the planned treatment beams and (b) in the setup of these patients on the treatment unit. To investigate how the systematic component of the latter errors can be reduced with an off-line decision protocol for setup corrections. METHODS AND MATERIALS: For 39 patients with CT planning, digitally-reconstructed radiographs (DRRs) were calculated for anterior-posterior and lateral beams. Retrospectively, the position of the visible anatomy relative to the planned isocenter was compared with the corresponding position on the digitized simulator radiographs using contour match software. The setup accuracy at the treatment unit relative to the simulator setup was measured for 40 patients for at least 5 fractions per patient in 2 orthogonal beams with the aid of an electronic portal imaging device (EPID). Setup corrections were applied, based on an off-line decision protocol, with parameters derived from knowledge of the random setup errors in the studied patient group. RESULTS: The standard deviations (SD) of the simulator setup errors relative to the CT planning setup in the lateral, longitudinal, and anterior-posterior directions were 4.0, 2.8, and 2.5 mm, respectively. The SD of rotations around the anterior-posterior axis was 1.6 degrees and around the left-right axis 1.3 degrees. The setup error at the treatment unit had a small random component in all three directions (1 SD = 2 mm). The systematic components were larger, particularly in the longitudinal direction (1 SD = 3.6 mm), but were reduced with the decision protocol to 1 SD < 2 mm with, on average, 0.6 setup correction per patient. CONCLUSION: Setup errors at the simulator, which become systematic errors if the simulation defines the reference setup, were comparable to the systematic setup errors at the treatment unit in case no off-line protocol would have been applied. Hence, the omission of a separate simulation step can reduce systematic errors as efficiently as the application of an off-line correction protocol during treatment. The random errors were sufficiently small to make an off-line protocol feasible.

Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck.

INTRODUCTION: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV). METHODS: For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose-volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans. RESULTS: In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%. CONCLUSION: For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.

Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study.

PURPOSE: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used. METHODS AND MATERIALS: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system. RESULTS: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs. CONCLUSIONS: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.

Beam intensity modulation for penumbra enhancement and field length reduction in lung cancer treatments: a dosimetric study.

BACKGROUND AND PURPOSE: In a recent treatment planning study, a previously published technique for superior-inferior field length reduction for prostate cancer patients, based on penumbra enhancement using static beam intensity modulation (BIM) with a multileaf collimator, was investigated for lung cancer treatments. For the patient group studied, the field lengths could be reduced by 1.4 cm and an average dose escalation of 6 Gy (maximum 16 Gy) appeared to be possible without any increase in the calculated risk of radiation pneumonitis. However, this planning study was performed with a treatment planning system that does not correctly account for the increased lateral secondary electron transport in lung tissue, resulting in too steep beam penumbrae. Therefore, prior to clinical implementation, an extensive dosimetric study was performed to evaluate and optimize BIM for penumbra enhancement and superior-inferior field length reduction in lung cancer treatments. MATERIALS AND METHODS: Film dosimetry was performed in several phantoms consisting of water equivalent and lung equivalent materials, both for a 6 and a 10 MV photon beam. Measured dose distributions were used to (i) adapt the BIM technique to properly account for increased lateral secondary electron transport, (ii) compare BIM dose distributions in lung material with dose distributions of standard treatment fields, and (iii) investigate the use of our treatment planning system for the design of BIM plans for lung cancer patients. RESULTS: Compared with our treatment planning study the superior and inferior boost fields, used in the BIM technique for penumbra enhancement, had to be longer and of a higher weight to compensate for the increased lateral secondary electron transport in lung tissue. With these modifications in the BIM technique, field lengths could indeed be reduced by 1.4 cm compared with treatment with standard fields, without the appearance of underdosages in the most superior and inferior target areas, whilst better sparing the healthy lung tissue. Practical rules were derived to use our treatment planning system for the design of BIM treatment plans. CONCLUSIONS: In spite of the increased lateral secondary electron transport in lung tissue, static BIM with a multileaf collimator may effectively be used for penumbra enhancement and superior-inferior field length reduction in lung cancer treatments.

A linear diode array (JFD-5) for match line in vivo dosimetry in photon and electron beams; evaluation for a chest wall irradiation technique.

BACKGROUND AND PURPOSE: In vivo dosimetry using thermoluminiscence detectors (TLD) is routinely performed in our institution to determine dose inhomogeneities in the match line region during chest wall irradiation. However, TLDs have some drawbacks: online in vivo dosimetry cannot be performed; generally, doses delivered by the contributing fields are not measured separately; measurement analysis is time consuming. To overcome these problems, the Joined Field Detector (JFD-5), a detector for match line in vivo dosimetry based on diodes, has been developed. This detector and its characteristics are presented. MATERIALS AND METHODS: The JFD-5 is a linear array of 5 p-type diodes. The middle three diodes, used to measure the dose in the match line region, are positioned at 5-mm intervals. The outer two diodes, positioned at 3-cm distance from the central diode, are used to measure the dose in the two contributing fields. For three JFD-5 detectors, calibration factors for different energies, and sensitivity correction factors for non-standard field sizes, patient skin temperature, and oblique incidence have been determined. The accuracy of penumbra and match line dose measurements has been determined in phantom studies and in vivo. RESULTS: Calibration factors differ significantly between diodes and between photon and electron beams. However, conversion factors between energies can be applied. The correction factor for temperature is 0.35%/ degrees C, and for oblique incidence 2% at maximum. The penumbra measured with the JFD-5 agrees well with film and linear diode array measurements. JFD-5 in vivo match line dosimetry reproducibility was 2.0% (1 SD) while the agreement with TLD was 0.999+/-0.023 (1 SD). CONCLUSION: The JFD-5 can be used for accurate, reproducible, and fast on-line match line in vivo dosimetry.

Film dosimetry in water in a 23 MV therapeutic photon beam.

The field size and water depth dependence of the measured optical density of Kodak XV-2 film, irradiated in a 23 MV photon beam has been investigated. The films were positioned in a water tank in a vertical plane containing the beam axis with the upper film edge parallel to the water surface at a depth of 0.3 mm. The observed field size and water depth dependence of the film sensitivity cannot be fully attributed to the usual variation of the photon spectrum with field size and water depth: measured optical densities do significantly depend on the amount of film material above the point of measurement and on the film orientation. A method for application of film for relative water dose measurements in a plane containing the beam axis in a 23 MV therapeutic photon beam is presented; the observed agreement between film and ionisation chamber measurements is very good: typically within 1% or 2 mm.