A comparison of the acute toxicity profile between two-dimensional and three-dimensional image-guided radiotherapy for postoperative prostate cancer.

AIMS: To compare acute gastrointestinal and genitourinary toxicity for patients positioned with an electronic portal imaging device (EPID) and patients positioned with kilovoltage cone beam computed tomography (CBCT) during postoperative prostate radiotherapy. MATERIALS AND METHODS: Between 1999 and April 2010, 196 prostate cancer patients were referred for postoperative salvage radiotherapy. Patient position was corrected using EPID (1999 to December 2006, n=116) or CBCT (January 2007 to present, n=80). The treatment technique, number of beams, dose prescription, dose computation algorithm and planning target volume margins were not altered over time. Grade 1-3 acute gastrointestinal and genitourinary toxicity were compared between the EPID group and the CBCT group. RESULTS: The incidence of grade 1 and 2 genitourinary toxicity was significantly reduced by 17 and 14%, respectively, in the CBCT group compared with the EPID group (P<0.05). This was mainly attributed to a decrease in the following grade 1 symptoms: frequency (P<0.05), nocturia (P=0.06) and urgency (P=0.07). Grade 2 incontinence (P=0.06) and frequency (P=0.06) were lower in the CBCT group. Grade 3 genitourinary toxicity was comparably low (EPID 3% versus CBCT 1%). There was no significant difference in gastrointestinal grade 1-2 toxicity between both groups. No grade 3 gastrointestinal toxicity was observed. CONCLUSIONS: Patient positioning with CBCT significantly reduces acute genitourinary toxicity compared with positioning with EPID.

Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and quality assurance of the clinical treatment planning system.

The purpose of this investigation was the verification of both the measured data and quality of the implementation of the add-on ModuLeaf miniature multileaf collimator (ML mMLC) into the clinical treatment planning system for conformal stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in the setup were first benchmarked with a set of measurements. A total ML mMLC transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and measured output factors (OFs) was within 2%. Correspondence between MC and measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5 x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution superposition algorithm) calculated dose distributions, using a gamma evaluation comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom. The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points not fulfilling gamma

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations.

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

MCDE: a new Monte Carlo dose engine for IMRT.

A new accurate Monte Carlo code for IMRT dose computations, MCDE (Monte Carlo dose engine), is introduced. MCDE is based on BEAMnrc/DOSXYZnrc and consequently the accurate EGSnrc electron transport. DOSXYZnrc is reprogrammed as a component module for BEAMnrc. In this way both codes are interconnected elegantly, while maintaining the BEAM structure and only minimal changes to BEAMnrc.mortran are necessary. The treatment head of the Elekta SLiplus linear accelerator is modelled in detail. CT grids consisting of up to 200 slices of 512 x 512 voxels can be introduced and up to 100 beams can be handled simultaneously. The beams and CT data are imported from the treatment planning system GRATIS via a DICOM interface. To enable the handling of up to 50 x 10(6) voxels the system was programmed in Fortran95 to enable dynamic memory management. All region-dependent arrays (dose, statistics, transport arrays) were redefined. A scoring grid was introduced and superimposed on the geometry grid, to be able to limit the number of scoring voxels. The whole system uses approximately 200 MB of RAM and runs on a PC cluster consisting of 38 1.0 GHz processors. A set of in-house made scripts handle the parallellization and the centralization of the Monte Carlo calculations on a server. As an illustration of MCDE, a clinical example is discussed and compared with collapsed cone convolution calculations. At present, the system is still rather slow and is intended to be a tool for reliable verification of IMRT treatment planning in the case of the presence of tissue inhomogeneities such as air cavities.

Validation and application of polymer gel dosimetry for the dose verification of an intensity-modulated arc therapy (IMAT) treatment.

Polymer gel dosimetry was used to assess an intensity-modulated arc therapy (IMAT) treatment for whole abdominopelvic radiotherapy. Prior to the actual dosimetry experiment, a uniformity study on an unirradiated anthropomorphic phantom was carried out. A correction was performed to minimize deviations in the R2 maps due to radiofrequency non-uniformities. In addition, compensation strategies were implemented to limit R2 deviations caused by temperature drift during scanning. Inter- and intra-slice R2 deviations in the phantom were thereby significantly reduced. This was verified in an investigative study where the same phantom was irradiated with two rectangular superimposed beams: structural deviations between gel measurements and computational results remained below 3% outside high dose gradient regions; the spatial shift in those regions was within 2.5 mm. When comparing gel measurements with computational results for the IMAT treatment, dose deviations were noted in the liver and right kidney, but the dose-volume constraints were met. Root-mean-square differences between both dose distributions were within 5% with spatial deviations not more than 2.5 mm. Dose fluctuations due to gantry angle discretization in the dose computation algorithm were particularly noticeable in the low-dose region.

Dose conformation in IMRT for head and neck tumors: which solution to apply?

At Ghent University Hospital, IMRT for head and neck cancer is routinely performed. The desired dose distribution is defined upfront as a range of acceptable doses assigned to each voxel of volumes of interest. It was found important to specify the range of acceptable doses separately to areas of the PTV either in or outside the buildup zone as well as to areas which do or do not intersect with PTV-dose limiting organs at risk (OAR). To avoid high doses at distance from the PTV, the creation of a "surrounding" OAR which is the whole scanned volume minus the PTV was found efficient, especially if inside this OAR, subvolumes were created at increasing distance from the PTV. By specifying inside these subvolumes maximum dose constraints which decreased with distance from the PTV, conformality is secured. The creation of these additional PTV and OAR subvolumes allows comprehensive and unambiguous definition of the range of acceptable doses and thereby avoids user-interactive assignment of weights to the terms of the objective function during optimization. The efficiency of inverse planning is highly improved. Its outcome is predictable, plan evaluation is objective as the plan either does or does not comply with the predefined range of acceptable doses. Accurate reporting of the planned dose distribution is facilitated by description of the dose range to all volumes. The expense of this procedure is modest and lays mostly 1) in the creation of the subvolumes, which can be done semi-automatically by modern image segmentation tools and 2) in the inclusion of constraints to all subvolumes into the objective function.

Evaluation of a leaf position optimization tool for intensity modulated radiation therapy of head and neck cancer.

BACKGROUND AND PURPOSE: Since 1996, patients are treated at Ghent University Hospital with a multi-segment technique using MultiLeaf Collimators. The segments were obtained by using the Beam's eye view projections of the planning target volume (PTV) and the organs at risk (OARs), after which the segments weights were optimized. To investigate if optimization of the leaf positions would further improve the intensity modulated radiation therapy (IMRT) plans, a tool optimizing leaf positions and segment weights simultaneously, was developed. This tool is called SOWAT, which is the acronym for segment outline and weight adapting tool. MATERIAL AND METHODS: The tool evaluates the effects of changing the position of each collimating leaf of all segments on the value of the objective function. Only changes that improve the value of the objective function are retained. Between December 1999 and January 2001, 30 head and neck patients were treated with IMRT. Two patient groups were distinguished: pharyngeal and laryngeal tumors (n=17) and sinonasal tumors (n=13). A specific set of physical endpoints was evaluated for each group. Dose statistics of the treatment plans without and with SOWAT were analyzed. RESULTS: When using SOWAT for the pharyngeal and laryngeal cases, the PTV dose homogeneity increased with a median of 11% (range 2-27%), while the maximum dose to the spinal cord was decreased for 14 of the 17 patients. In four plans where parotid function preservation was a goal, the parotid mean dose was lower than 26 Gy in one plan without SOWAT, and in four plans with SOWAT. For the sinonasal tumors, the PTV dose homogeneity increased with a median of 7% (range 1-14%). SOWAT lowered the mean dose to 53 of the 63 optic pathway structures (retina, optic nerve and optic chiasm). SOWAT leaves the number of segments unchanged and has little or no effect on the delivery time. CONCLUSIONS: SOWAT is a powerful tool to perform the final optimization of IMRT plans, without increasing the complexity of the plan or the delivery time.

Leaf position optimization for step-and-shoot IMRT.

PURPOSE: To describe the theoretical basis, the algorithm, and implementation of a tool that optimizes segment shapes and weights for step-and-shoot intensity-modulated radiation therapy delivered by multileaf collimators. METHODS AND MATERIALS: The tool, called SOWAT (Segment Outline and Weight Adapting Tool) is applied to a set of segments, segment weights, and corresponding dose distribution, computed by an external dose computation engine. SOWAT evaluates the effects of changing the position of each collimating leaf of each segment on an objective function, as follows. Changing a leaf position causes a change in the segment-specific dose matrix, which is calculated by a fast dose computation algorithm. A weighted sum of all segment-specific dose matrices provides the dose distribution and allows computation of the value of the objective function. Only leaf position changes that comply with the multileaf collimator constraints are evaluated. Leaf position changes that tend to decrease the value of the objective function are retained. After several possible positions have been evaluated for all collimating leaves of all segments, an external dose engine recomputes the dose distribution, based on the adapted leaf positions and weights. The plan is evaluated. If the plan is accepted, a segment sequencer is used to make the prescription files for the treatment machine. Otherwise, the user can restart SOWAT using the new set of segments, segment weights, and corresponding dose distribution. The implementation was illustrated using two example cases. The first example is a T1N0M0 supraglottic cancer case that was distributed as a multicenter planning exercise by investigators from Rotterdam, The Netherlands. The exercise involved a two-phase plan. Phase 1 involved the delivery of 46 Gy to a concave-shaped planning target volume (PTV) consisting of the primary tumor volume and the elective lymph nodal regions II-IV on both sides of the neck. Phase 2 involved a boost of 24 Gy to the primary tumor region only. SOWAT was applied to the Phase 1 plan. Parotid sparing was a planning goal. The second implementation example is an ethmoid sinus cancer case, planned with the intent of bilateral visus sparing. The median PTV prescription dose was 70 Gy with a maximum dose constraint to the optic pathway structures of 60 Gy. RESULTS: The initial set of segments, segment weights, and corresponding dose distribution were obtained, respectively, by an anatomy-based segmentation tool, a segment weight optimization tool, and a differential scatter-air ratio dose computation algorithm as external dose engine. For the supraglottic case, this resulted in a plan that proved to be comparable to the plans obtained at the other institutes by forward or inverse planning techniques. After using SOWAT, the minimum PTV dose and PTV dose homogeneity increased; the maximum dose to the spinal cord decreased from 38 Gy to 32 Gy. The left parotid mean dose decreased from 22 Gy to 19 Gy and the right parotid mean dose from 20 to 18 Gy. For the ethmoid sinus case, the target homogeneity increased by leaf position optimization, together with a better sparing of the optical tracts. CONCLUSIONS: By using SOWAT, the plans improved with respect to all plan evaluation end points. Compliance with the multileaf collimator constraints is guaranteed. The treatment delivery time remains almost unchanged, because no additional segments are created.

An anatomy-based beam segmentation tool for intensity-modulated radiation therapy and its application to head-and-neck cancer.

PURPOSE: In segmental intensity-modulated radiation therapy (IMRT), the beam fluences result from superposition of unmodulated beamlets (segments). In the inverse planning approach, segments are a result of ''clipping'' intensity maps. At Ghent University Hospital, segments are created by an anatomy-based segmentation tool (ABST). The objective of this report is to describe ABST. METHODS AND MATERIALS: For each beam direction, ABST generates segments by a multistep procedure. During the initial steps, beam's eye view (BEV) projections of the planning target volumes (PTVs) and organs at risk (OARs) are generated. These projections are used to make a segmentation grid with negative values across the expanded OAR projections and positive values elsewhere inside the expanded PTV projections. Outside these regions, grid values are set to zero. Subsequent steps transform the positive values of the segmentation grid to increase with decreasing distance to the OAR projections and to increase with longer pathlengths measured along rays from their entrance point through the skin contours to their respective grid point. The final steps involve selection of iso-value lines of the segmentation grid as segment outlines which are transformed to leaf and jaw positions of a multileaf collimator (MLC). Segment shape approximations, if imposed by MLC constraints, are done in a way that minimizes overlap between the expanded OAR projections and the segment aperture. RESULTS: The ABST procedure takes about 3 s/segment on a Compaq Alpha XP900 workstation. In IMRT planning problems with little complexity, such as laryngeal (example shown) or thyroid cancer, plans that are in accordance with the clinical protocol can be generated by weighting the segments generated by ABST without further optimization of their shapes. For complex IMRT plans such as paranasal sinus cancer (not shown), ABST generates a start assembly of segments from which the shapes and weights are further optimized. CONCLUSIONS: ABST is a fast procedure to generate a set of segments for IMRT planning. The plan is finalized by assigning weights to the segments or by direct optimization of segment shapes and weights. ABST allows us to avoid the step of translating optimized intensity maps to sequences of segments.

An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE: To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS: The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION: Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Combining the advantages of step-and-shoot and dynamic delivery of intensity-modulated radiotherapy by interrupted dynamic sequences.

PURPOSE: A hybrid between step-and-shoot and dynamic operation, called interrupted dynamic sequences, was investigated for prostate intensity-modulated radiotherapy (IMRT) delivered by a multisegment close-in technique. The new delivery mode was compared to the step-and-shoot mode concerning dose distribution. METHODS AND MATERIALS: Segments suitable for dynamic transition were selected using a system of segment classes. Transitions were only allowed between two segments of the same class, keeping intended sharp in-field dose gradients unchanged. Delivery was performed by an Elekta SLiplus (Crawley, UK) linear accelerator equipped with a dynamic multileaf collimator (MLC). Because no modeling of the dose during the transitions is made, accurate dose measurements were performed. Dose profiles were measured using a linear ion chamber array (LA48, PTW-Freiburg). The suitability of this detector for measurements in sharp dose gradients was investigated first. In addition, field flatness was examined for segments with a low monitor unit (MU) count. Uncertainties in dose output were investigated using an ionization chamber (30001, PTW-Freiburg). RESULTS: Because linear array measured penumbrae are only slightly broader (< or = 0.4 mm for MLC collimated field) than those obtained using a diamond detector, the array is a good device for profile measurements. Uncertainties related with the use of low MU beam segments are very small (< 1% for segments of minimum 3 MU), giving no contra-evidence for the step-and-shoot mode. Interrupted dynamic sequences are shown to introduce only small dosimetric differences as compared to the step-and-shoot delivery. CONCLUSION: Both delivery modes, step-and-shoot and interrupted dynamic sequences, result in similar dose distributions for the forward planned prostate class solution.

Radiotherapy of prostate cancer with or without intensity modulated beams: a planning comparison.

PURPOSE: To evaluate whether intensity modulated radiotherapy (IMRT) by static segmented beams allows the dose to the main portion of the prostate target to escalate while keeping the maximal dose at the anterior rectal wall at 72 Gy. The value of such IMRT plans was analyzed by comparison with non-IMRT plans using the same beam incidences. METHODS AND MATERIALS: We performed a planning study on the CT data of 32 consecutive patients with localized adenocarcinoma of the prostate. Three fields in the transverse plane with gantry angles of 0 degrees, 116 degrees, and 244 degrees were isocentered at the center of gravity of the target volume (prostate and seminal vesicles). The geometry of the beams was determined by beam's eye view autocontouring of the target volume with a margin of 1.5 cm. In study 1, the beam weights were determined by a human planner (3D-man) or by computer optimization using a biological objective function with (3D-optim-lim) or without (3D-optim-unlim) a physical term to limit target dose inhomogeneity. In study 2, the 3 beam incidences mentioned above were used and in-field uniform segments were added to allow IMRT. Plans with (IMRT-lim) or without (IMRT-unlim) constraints on target dose inhomogeneity were compared. In the IMRT-lim plan, target dose inhomogeneity was constrained between 15% and 20%. After optimization, plans in both studies were normalized to a maximal rectal dose of 72 Gy. Biological (tumor control probability [TCP], normal tissue complication probability [NTCP]) and physical indices for tumor control and normal tissue complication probabilities were computed, as well as the probability of the uncomplicated local control (P+). RESULTS: The IMRT-lim plan was superior to all other plans concerning TCP (p < 0.0001). The IMRT-unlim plan had the worst TCP. Within the 3D plans, the 3D-optim-unlim had the best TCP, which was significantly different from the 3D-optim-lim plan (p = 0.0003). For rectal NTCP, both IMRT plans were superior to all other plans (p < 0.0001). The IMRT-unlim plan was significantly better than the IMRT-lim plan (p < 0.0001). Again, 3D-optim-unlim was superior to the other 3D plans (p < 0. 0007). Physical endpoints for target showed the mean minimal target dose to be the lowest in the IMRT-unlim plan, caused by a large target dose inhomogeneity (TDI). Medial target dose, 90th percentile, and maximal target dose were significantly higher in both IMRT plans. Physical endpoints for the rectum showed the IMRT-unlim plan to be superior compared to all other plans. There was a strong correlation between the 65th percentile (Rp65) and rectal NTCP (correlation coefficient > or =89%). For bladder, maximal bladder dose was significantly higher in the IMRT-unlim plan compared to all other plans (p < or = 0.0001).P+ was significantly higher in both IMRT-plans than in all other plans. The 3D-optim-unlim plan was significantly better than the two other 3D plans (p < 0.0001). CONCLUSION: IMRT significantly increases the ratio of TCP over NTCP of the rectum in the treatment of prostate cancer. However, constraints for TDI are needed, because a high degree of TDI reduced minimal target dose. IMRT improved uncomplicated local control probability. In our department, IMRT by static segmented beams is planned and delivered in a cost-effective way. IMRT-lim has replaced non-modulated conformal radiotherapy as the standard treatment for prostate cancer.

Optimization of beam weights in conformal radiotherapy planning of stage III non-small cell lung cancer: effects on therapeutic ratio.

PURPOSE: To evaluate the effects of beam weight optimization for 3D conformal radiotherapy plans, with or without beam intensity modulation, in Stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Ten patients with Stage III NSCLC were planned using a conventional 3D technique and a technique involving noncoplanar beam intensity modulation (BIM). Two planning target volumes (PTVs) were defined: PTV1 included macroscopic tumor volume and PTV2 included macroscopic and microscopic tumor volume. Virtual simulation defined the beam shapes and incidences as well as the wedge orientations (3D) and segment outlines (BIM). Weights of wedged beams, unwedged beams, and segments were determined by human trial and error for the 3D-plans (3D-manual), by a standard weight table (SWT) for the BIM-plans (BIM-SWT) and by optimization (3D-optimized and BIM-optimized) using an objective function with a biological and a physical component. The resulting non-optimized and optimized dose distributions were compared, using physical endpoints, after normalizing the median dose of PTV1 to 80 Gy. RESULTS: Optimization improved dose homogeneity at the target for 3D- and BIM-plans and the minimum dose at PTV1. The minimum dose at PTV2 was decreased by optimization especially in 3D-plans. After optimization, the dose-volume histograms (DVHs) of lung and heart were shifted to lower doses for 80-90% of the organ volume. Since lung is the dose-limiting organ in Stage III NSCLC, an increased minimum dose at PTV1 together with a decreased dose at the main lung volume suggests an improved therapeutic ratio. Optimization allows 10% dose escalation for 3D-plans and 20% for BIM-plans at isotoxicity levels of lung and spinal cord. Upon dose escalation, esophagus may become the dose-limiting structure when PTV1 extends close to the esophagus. CONCLUSIONS: Optimization using a biophysical objective function allowed an increase of the therapeutic ratio of radiotherapy planning for Stage III NSCLC.

Validation of MR-based polymer gel dosimetry as a preclinical three-dimensional verification tool in conformal radiotherapy.

The aim of this work was to investigate MR-based polymer gel dosimetry as a three-dimensional (3D) dosimetry technique in conformal radiotherapy. A cylindrical container filled with polymer gel was placed in a water-filled torso phantom to verify a treatment plan for the conformal irradiation of a mediastinal tumor located near the esophagus. Magnetic resonance spin-spin relaxation rate images were acquired and, after calibration, converted to absorbed dose distributions. The dose maps were compared with dose distributions measured using radiographic film. The average root-mean-square structural deviation, for the complete dose distribution, amounted to less than 3% between gel and film dose maps. It may be expected that MR gel dosimetry will become a valuable tool in the verification of 3D dose distributions. The influence of imaging artifacts arising from eddy currents, temperature drift during scanning, and B1 field inhomogeneity on the dose maps was taken into account and minimized.

Clinical delivery of intensity modulated conformal radiotherapy for relapsed or second-primary head and neck cancer using a multileaf collimator with dynamic control.

BACKGROUND AND PURPOSE: Concave dose distributions generated by intensity modulated radiotherapy (IMRT) were applied to re-irradiate three patients with pharyngeal cancer. PATIENTS, MATERIALS AND METHODS: Conventional radiotherapy for oropharyngeal (patients 1 and 3) or nasopharyngeal (patient 2) cancers was followed by relapsing or new tumors in the nasopharynx (patients 1 and 2) and hypopharynx (patient 3). Six non-opposed coplanar intensity modulated beams were generated by combining non-modulated beamparts with intensities (weights) obtained by minimizing a biophysical objective function. Beamparts were delivered by a dynamic MLC (Elekta Oncology Systems, Crawley, UK) forced in step and shoot mode. RESULTS AND CONCLUSIONS: Median PTV-doses (and ranges) for the three patients were 73 (65-78), 67 (59-72) and 63 (48-68) Gy. Maximum point doses to brain stem and spinal cord were, respectively, 67 Gy (60% of volume below 30 Gy) and 32 Gy (97% below 10 Gy) for patient 1; 60 Gy (69% below 30 Gy) and 34 Gy (92% below 10 Gy) for patient 2 and 21 Gy (96% below 10 Gy) at spinal cord for patient 3. Maximum point doses to the mandible were 69 Gy for patient 1 and 64 Gy for patient 2 with, respectively, 66 and 92% of the volume below 20 Gy. A treatment session, using the dynamic MLC, was finished within a 15-min time slot.

Postoperative radiotherapy of paranasal sinus tumours: a challenge for intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is used in our department for treatment of paranasal sinuses. We describe the methodology that was developed together with the clinical implementation, illustrated by a case report. MATERIAL AND METHODS: Patient history, treatment and short follow-up are described. An IMRT, obtained by superposition of static beam segments was implemented. Electronic portal images, compared to digitally reconstructed radiographs (DRR) were used to evaluate and adjust patient positioning. RESULTS, DISCUSSION AND CONCLUSION: IMRT is an appropriate and feasible treatment technique for head and neck cancer in anatomical regions that are difficult to treat. A high tumour dose can be combined with a good sparing of the surrounding organs at risk (OAR's).

Inhomogeneous target-dose distributions: a dimension more for optimization?

PURPOSE: To evaluate if the use of inhomogeneous target-dose distributions, obtained by 3D conformal radiotherapy plans with or without beam intensity modulation, offers the possibility to decrease indices of toxicity to normal tissues and/or increase indices of tumor control stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Ten patients with stage III NSCLC were planned using a conventional 3D technique and a technique involving noncoplanar beam intensity modulation (BIM). Two planning target volumes (PTVs) were defined: PTV1 included macroscopic tumor volume and PTV2 included macroscopic and microscopic tumor volume. Virtual simulation defined the beam shapes and incidences as well as the wedge orientations (3D) and segment outlines (BIM). Weights of wedged beams, unwedged beams, and segments were determined by optimization using an objective function with a biological and a physical component. The biological component included tumor control probability (TCP) for PTV1 (TCP1), PTV2 (TCP2), and normal tissue complication probability (NTCP) for lung, spinal cord, and heart. The physical component included the maximum and minimum dose as well as the standard deviation of the dose at PTV1. The most inhomogeneous target-dose distributions were obtained by using only the biological component of the objective function (biological optimization). By enabling the physical component in addition to the biological component, PTV1 inhomogeneity was reduced (biophysical optimization). As indices for toxicity to normal tissues, NTCP-values as well as maximum doses or dose levels to relevant fractions of the organ's volume were used. As indices for tumor control, TCP-values as well as minimum doses to the PTVs were used. RESULTS: When optimization was performed with the biophysical as compared to the biological objective function, the PTV1 inhomogeneity decreased from 13 (8-23)% to 4 (2-9)% for the 3D-(p = 0.00009) and from 44 (33-56)% to 20 (9-34)% for the BIM plans (p < 0. 00001). Minimum PTV1 doses (expressed as the lowest voxel-dose) were similar for both objective functions. The mean and maximum target doses were significantly higher with biological optimization for 3D as well as for BIM (all p values < 0.001). Tumor control probability (estimated by TCP1 x TCP2) was 4.7% (3D) and 6.2% (BIM) higher for biological optimization (p = 0.01 and p = 0.00002 respectively). NTCP(lung) as well as the percentage of lung volume exceeding 20 Gy was higher with the use of the biophysical objective function. NTCP(heart) was also higher with the use of the biophysical objective function. The percentage of heart volume exceeding 40 Gy tended to be higher but the difference was not significant. For spinal cord, the maximum dose as well as NTCP(cord) were similar for 3D plans (D(max): p = 0.04; NTCP: p = 0.2) but were significantly lower for BIM (D(max): p = 0.002; NTCP: p = 0.008) if the biophysical objective function was used. CONCLUSIONS: When using conventional 3D techniques, inhomogeneous dose distributions offer the potential to further increase the probability of uncomplicated local control. When using techniques as BIM that would lead to large escalation of the median and maximum target doses, it seems indicated to limit target-dose inhomogeneity to avoid dose levels that are so high that the safety becomes questionable.

Conformal radiotherapy of Stage III non-small cell lung cancer: a class solution involving non-coplanar intensity-modulated beams.

PURPOSE: We developed a semiautomatic class solution to irradiate centrally located Stage III non-small cell lung cancer (NSCLC), involving a beam intensity modulation technique and optimization using a biophysical cost function. METHODS AND MATERIALS: Treatment for 10 patients with Stage III NSCLC was planned, using a conventional three- or four-beam three-dimensional (3D) technique and two techniques involving, respectively, seven (BIM1) and five (BIM2) noncoplanar beam incidences with intensity modulation. Two planning target volumes were defined: PTV1 included macroscopic tumor volume and PTV2 included macroscopic and microscopic disease. Beams were divided into beam parts (segments) and their outlines were defined during virtual simulation. Optimization using a biophysical cost function determined beam weights, segment weights, and wedge angles. Biological end points included tumor control probability of both target volumes (TCP1 and TCP2) and normal tissue complication probability (NTCP) of heart, lung, and spinal cord. The resulting uncomplicated local control probability (UCLP) was calculated. Physical end points included dose at PTV1 expressed as a dose minimum and dose maximum. Target-dose inhomogeneity was constrained in all plans. RESULTS: Concerning tumor evaluation, TCP1 was 74% (range 54-89%) for the 3D plan, 78.0% (range 62-94%) for BIM1, and 86.0% (range 59-93%) for BIM2. TCP1*TCP2 was, respectively, 67.0% (range 39-81%), 73.0% (range 56-94%), and 81.0% (range 54-93%). Minimum doses to PTV1 were 85, 80, and 88 Gy with the three respective techniques, while dose maxima were 89, 101, and 100 Gy. NTCPs of lung were 45.0% (range 11-75%) for 3D, 19.5% (range 8-59%) for BIM1, and 24.5% (range 3-61%) for BIM2. NTCPs of heart and spinal cord were comparable for all techniques. ULCPs were 37.0% (range 9-73%), 52.5% (range 22-86%), and 60.0% (range 20-85%), respectively. Applying physical limits to ensure clinical safety, minimum doses at PTV1 were recalculated. These were 72, 71, and 74 Gy for 3D, BIM1, and BIM2, respectively. CONCLUSION: The BIM2 plan is a candidate class solution for dose escalation studies in centrally located Stage III NSCLC.

Non-coplanar beam intensity modulation allows large dose escalation in stage III lung cancer.

PURPOSE: To evaluate the feasibility of dose escalation in stage III non-small cell lung cancer, we compared standard coplanar (2D) with non-coplanar beam arrangements, without (3D) and with beam intensity modulation (3D-BIM). MATERIALS AND METHODS: This study was a planning effort performed on a non-selected group of 10 patients. Starting from a serial CT scan, treatment planning was performed using Sherouse's GRATIS 3D planning system. Two target volumes were defined; gross tumor volume (GTV) defined a high-dose target volume that had to receive a dose of at least 80 Gy and GTV plus the lymph node regions with >10% probability of invasion defined an intermediate-dose target volume (GTV + N). It was our intention to irradiate GTV + N up to 56 Gy or more. If the prescribed doses on GTV and GTV + N could not be reached with either the 2D or 3D technique, a 3D-BIM plan was performed. The 3D-BIM plan was a class solution involving identical gantry angles, segment arrangements and relative segment weights for all patients. Dose volume histograms for GTV, GTV + N, lung and spinal cord were calculated. Criteria for tolerance were met if no points inside the spinal cord exceeded 50 Gy and if at least 50% of the lung volume received less than 20 Gy. Under these constraints, maximal achievable doses to GTV and GTV + N were calculated. RESULTS: In all 2D plans, spinal cord was the limiting factor and the prescribed doses for GTV and GTV + N could not be reached in any patient. The non-coplanar 3D plan resulted in a satisfying solution in 4 out of 10 patients under the same constraints. In comparison with 2D, the minimum dose in GTV + N was increased. Six patients had to be planned with the 3D-BIM technique. The theoretical minimum dose to GTV + N ranged between 56 and 98 Gy. The delivery of 80 Gy or more to GTV was possible in all patients. For a minimal dose of 80 Gy to GTV, the maximal dose to any point of the spinal cord varied between 27 and 46 Gy. The lung volume receiving more than 20 Gy ranged from 26 to 46%. CONCLUSION: The potential of 3D-BIM for dose escalation is explained as follows: (i) compared to other planning techniques, a larger amount of lung tissue can be spared by using beam directions that are well-aligned with the mediastinal structures. Such beam directions have narrow angles with the sagittal plane; (ii) dividing all beams into segments with well-specified geometrical restrictions in relation to the spinal cord and well-defined relative weights results in a lower dose to the spinal cord.