18F-FDG-PET guided vs whole tumour radiotherapy dose escalation in patients with locally advanced non-small cell lung cancer (PET-Boost): Results from a randomised clinical trial.

BACKGROUND AND PURPOSE: We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an 18F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer. MATERIALS AND METHODS: Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II 'pick-the-winner' design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year. CLINICALTRIALS: gov:NCT01024829. RESULTS: 150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91-100) in whole tumour group, and 91 % (95 %CI 82-100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group. CONCLUSION: Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.

Alpha/beta ratio for normal lung tissue as estimated from lung cancer patients treated with stereotactic body and conventionally fractionated radiation therapy.

PURPOSE: To estimate the α/ß ratio for which the dose-dependent lung perfusion reductions for stereotactic body radiation therapy (SBRT) and conventionally fractionated radiation therapy (CFRT) are biologically equivalent. METHODS AND MATERIALS: The relations between local dose and perfusion reduction 4 months after treatment in lung cancer patients treated with SBRT and CFRT were scaled according to the linear-quadratic model using α/ß ratios from 0 Gy to ∞ Gy. To test for which α/ß ratio both treatments have equal biological effect, a 5-parameter logistic model was optimized for both dose-effect relationships simultaneously. Beside the α/ß ratio, the other 4 parameters were d50, the steepness parameter k, and 2 parameters (MSBRT and MCFRT) representing the maximal perfusion reduction at high doses for SBRT and CFRT, respectively. RESULTS: The optimal fitted model resulted in an α/ß ratio of 1.3 Gy (0.5-2.1 Gy), MSBRT=42.6% (40.4%-44.9%), MCFRT=66.9% (61.6%-72.1%), d50=35.4 Gy (31.5-9.2 Gy), and k=2.0 (1.7-2.3). CONCLUSIONS: An equal reduction of lung perfusion in lung cancer was observed in SBRT and CFRT if local doses were converted by the linear-quadratic model with an α/ß ratio equal to 1.3 Gy (0.5-2.1 Gy).

Local dose-effect relations for lung perfusion post stereotactic body radiotherapy.

PURPOSE: To model the local dose-effect relation for lung perfusion reduction in lung cancer patients treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty-two patients having upper-lobe peripheral tumours <5 cm treated with SBRT (3×18 Gy) underwent single-photon emission computed-tomography (SPECT) scans to measure the lung perfusion 2 weeks pre-SBRT, 4-months post-SBRT, and for 8 patients 15-months post-SBRT. The relation between the calculated relative local perfusion reduction and the normalised total dose (α/ß=3 Gy) at 4-months post-SBRT was modeled by 3-parameter logistic model and 2-parameter linear-maximum model. RESULTS: The relation between local dose and perfusion reduction at 4-months post-SBRT showed a maximum effect of 42.6% at doses >100 Gy and was best described by the logistic model with parameters (95% CI): M=42.6% (40.7-44.6), D50=28.7 Gy (26.3-31.1) and k=2.2 (1.8-2.5). A significant increase of this maximum effect to 65.2% was found at 15-months post-SBRT. CONCLUSIONS: The relation between local dose and perfusion reduction in patients treated with SBRT can be modeled by a 3-parameter logistic model. This demonstrated relationship 4-months post-SBRT approaches a plateau for doses >100 Gy, where 90% of the maximum lung-perfusion reduction is observed at NTD=78 Gy. A further perfusion reduction compared to 4-months post-SBRT was observed fifteen months post-SBRT.

Volumetric-modulated arc therapy for stereotactic body radiotherapy of lung tumors: a comparison with intensity-modulated radiotherapy techniques.

PURPOSE: To demonstrate the potential of volumetric-modulated arc therapy (VMAT) compared with intensity-modulated radiotherapy (IMRT) techniques with a limited number of segments for stereotactic body radiotherapy (SBRT) for early-stage lung cancer. METHODS AND MATERIALS: For a random selection of 27 patients eligible for SBRT, coplanar and noncoplanar IMRT and coplanar VMAT (using SmartArc) treatment plans were generated in Pinnacle(3) and compared. In addition, film measurements were performed using an anthropomorphic phantom to evaluate the skin dose for the different treatment techniques. RESULTS: Using VMAT, the delivery times could be reduced to an average of 6.6 min compared with 23.7 min with noncoplanar IMRT. The mean dose to the healthy lung was 4.1 Gy for VMAT and noncoplanar IMRT and 4.2 Gy for coplanar IMRT. The volume of healthy lung receiving>5 Gy and >20 Gy was 18.0% and 5.4% for VMAT, 18.5% and 5.0% for noncoplanar IMRT, and 19.4% and 5.7% for coplanar IMRT, respectively. The dose conformity at 100% and 50% of the prescribed dose of 54 Gy was 1.13 and 5.17 for VMAT, 1.11 and 4.80 for noncoplanar IMRT and 1.12 and 5.31 for coplanar IMRT, respectively. The measured skin doses were comparable for VMAT and noncoplanar IMRT and slightly greater for coplanar IMRT. CONCLUSIONS: Coplanar VMAT for SBRT for early-stage lung cancer achieved plan quality and skin dose levels comparable to those using noncoplanar IMRT and slightly better than those with coplanar IMRT. In addition, the delivery time could be reduced by ≤70% with VMAT.

Effects of respiration-induced density variations on dose distributions in radiotherapy of lung cancer.

PURPOSE: To determine the effect of respiration-induced density variations on the estimated dose delivered to moving structures and, consequently, to evaluate the necessity of using full four-dimensional (4D) treatment plan optimization. METHODS AND MATERIALS: In 10 patients with large tumor motion (median, 1.9 cm; range, 1.1-3.6 cm), the clinical treatment plan, designed using the mid-ventilation ([MidV]; i.e., the 4D-CT frame closest to the time-averaged mean position) CT scan, was recalculated on all 4D-CT frames. The cumulative dose was determined by transforming the doses in all breathing phases to the MidV geometry using deformable registration and then averaging the results. To determine the effect of density variations, this cumulative dose was compared with the accumulated dose after similarly deforming the planned (3D) MidV-dose in each respiratory phase using the same transformation (i.e., "blurring the dose"). RESULTS: The accumulated tumor doses, including and excluding density variations, were almost identical. Relative differences in the minimum gross tumor volume (GTV) dose were less than 2% for all patients. The relative differences were even smaller in the mean lung dose and the V20 (<0.5% and 1%, respectively). CONCLUSIONS: The effect of respiration-induced density variations on the dose accumulated over the respiratory cycle was very small, even in the presence of considerable respiratory motion. A full 4D-dose calculation for treatment planning that takes into account such density variations is therefore not required. Planning using the MidV-CT derived from 4D-CT with an appropriate margin for geometric uncertainties is an accurate and safe method to account for respiration-induced anatomy variations.

Comparison of different strategies to use four-dimensional computed tomography in treatment planning for lung cancer patients.

PURPOSE: To discuss planning target volumes (PTVs) based on internal target volume (PTVITV), exhale-gated radiotherapy (PTVGating), and a new proposed midposition (PTVMidP; time-weighted mean tumor position) and compare them with the conventional free-breathing CT scan PTV (PTVConv). METHODS AND MATERIALS: Respiratory motion induces systematic and random geometric uncertainties. Their contribution to the clinical target volume (CTV)-to-PTV margins differs for each PTV approach. The uncertainty margins were calculated using a dose-probability-based margin recipe (based on patient statistics). Tumor motion in four-dimensional CT scans was determined using a local rigid registration of the tumor. Geometric uncertainties for interfractional setup errors and tumor baseline variation were included. For PTVGating, the residual motion within a 30% gating (time) window was determined. The concepts were evaluated in terms of required CTV-to-PTV margin and PTV volume for 45 patients. RESULTS: Over the patient group, the PTVITV was on average larger (+6%) and the PTVGating and PTVMidP smaller (-10%) than the PTVConv using an off-line (bony anatomy) setup correction protocol. With an on-line (soft tissue) protocol the differences in PTV compared with PTVConv were +33%, -4%, and 0, respectively. CONCLUSIONS: The internal target volume method resulted in a significantly larger PTV than conventional CT scanning. The exhale-gated and mid-position approaches were comparable in terms of PTV. However, mid-position (or mid-ventilation) is easier to use in the clinic because it only affects the planning part of treatment and not the delivery.

Mid-ventilation CT scan construction from four-dimensional respiration-correlated CT scans for radiotherapy planning of lung cancer patients.

PURPOSE: Four-dimensional (4D) respiration-correlated imaging techniques can be used to obtain (respiration) artifact-free computed tomography (CT) images of the thorax. Current radiotherapy planning systems, however, do not accommodate 4D-CT data. The purpose of this study was to develop a simple, new concept to incorporate patient-specific motion information, using 4D-CT scans, in the radiotherapy planning process of lung cancer patients to enable smaller error margins. METHODS AND MATERIALS: A single CT scan was selected from the 4D-CT data set. This scan represented the tumor in its time-averaged position over the respiratory cycle (the mid-ventilation CT scan). To select the appropriate CT scan, two methods were used. First, the three-dimensional tumor motion was analyzed semiautomatically to calculate the mean tumor position and the corresponding respiration phase. An alternative automated method was developed to select the correct CT scan using the diaphragm motion. RESULTS: Owing to hysteresis, mid-ventilation selection using the three-dimensional tumor motion had a tumor position accuracy (with respect to the mean tumor position) better than 1.1 +/- 1.1 mm for all three directions (inhalation and exhalation). The accuracy in the diaphragm motion method was better than 1.1 +/- 1.1 mm. Conventional free-breathing CT scanning had an accuracy better than 0 +/- 3.9 mm. The mid-ventilation concept can result in an average irradiated volume reduction of 20% for tumors with a diameter of 40 mm. CONCLUSION: Tumor motion and the diaphragm motion method can be used to select the (artifact-free) mid-ventilation CT scan, enabling a significant reduction of the irradiated volume.

Impact of geometrical uncertainties on 3D CRT and IMRT dose distributions for lung cancer treatment.

PURPOSE: To quantify the effect of set-up errors and respiratory motion on dose distributions for non-small cell lung cancer (NSCLC) treatment. METHODS AND MATERIALS: Irradiations of 5 NSCLC patients were planned with 3 techniques, two (conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT1)) with a homogeneous dose in the planning target volume (PTV) and a third (IMRT2) with dose heterogeneity. Set-up errors were simulated for gross target volume (GTV) and organs at risk (OARs). For the GTV, the respiration was also simulated with a periodical motion around a varying average. Two configurations were studied for the breathing motion, to describe the situations of free-breathing (FB) and respiration-correlated (RC) CT scans, each with 2 amplitudes (5 and 10 mm), thus resulting in 4 scenarios (FB_5, FB_10, RC_5 and RC_10). Five thousand treatment courses were simulated, producing probability distributions for the dosimetric parameters. RESULTS: For CRT and IMRT1, RC_5, RC_10 and FB_5 were associated with a small degradation of the GTV coverage. IMRT2 with FB_10 showed the largest deterioration of the GTV dosimetric indices, reaching 7% for Dmin at the 95% probability level. Removing the systematic error due to the periodic breathing motion was advantageous for a 10 mm respiration amplitude. The estimated probability of radiation pneumonitis and acute complication for the esophagus showed limited sensitivity to geometrical uncertainties. Dmax in the spinal cord and the parameters predicting the risk of late esophageal toxicity were associated to a probability up to 50% of violating the dose tolerances. CONCLUSIONS: Simulating the effect of geometrical uncertainties on the individual patient plan should become part of the standard pre-treatment verification procedure.

Intensity-modulated radiotherapy of breast cancer using direct aperture optimization.

BACKGROUND AND PURPOSE: To design a clinically reliable and efficient step-and-shoot IMRT delivery technique for the treatment of breast cancer using direct aperture optimization (DAO). Using DAO, segments are created and optimized within the same optimization process. PATIENTS AND METHODS: The DAO technique implemented in the Pinnacle treatment planning system, which is called direct machine parameter optimization (DMPO), was used to generate IMRT plans for twelve breast cancer patients. The prescribed dose was 50 Gy. Two DMPO plans were generated. The first approach uses DMPO only; the second technique combines DMPO with two predefined segments (DMPO(segm)), having shapes identical to the conventional tangential fields. The weight of these predefined segments is optimized simultaneously with DMPO. The DMPO plans were compared with normal two-step (TS) IMRT, creating segments after optimizing the intensity. RESULTS: Dose homogeneity within the target volume was 4.8+/-0.6, 4.3+/-0.5 and 3.8+/-0.5 Gy for the TS, DMPO and DMPO(segm) plans, respectively. Comparing the IMRT plans with an idealized dose distribution obtained using only beamlet optimization, the degradation of the dose distribution was less for the DMPO plans compared with the two-step IMRT approach. Furthermore, this degradation was similar for all patients, while for the two-step IMRT approach it was patient specific. CONCLUSIONS: An efficient step-and-shoot IMRT solution was developed for the treatment of breast cancer using DMPO combined with two predefined segments.

The sensitivity of dose distributions for organ motion and set-up uncertainties in prostate IMRT.

BACKGROUND AND PURPOSE: To determine the effect of organ motion and set-up uncertainties on IMRT dose distributions for prostate. METHODS: For five patients, IMRT techniques were designed to irradiate the CTV (prostate plus seminal vesicles). Technique I delivered 78 Gy to PTV1 (CTV+10 mm margin). Technique II delivered 68 Gy to PTV1, and a 10 Gy boost to PTV2 (CTV+an anisotropic margin of 0 to 5 mm). Technique III delivered 68 Gy to PTV1 and simultaneously 78 Gy to PTV2. Uncertainties were simulated using population statistics of organ motion and set-up accuracy. The average TCP (TCPpop) of the CTV and average NTCP (NTCPpop) of the rectal wall were calculated. RESULTS: The planning TCP was a good predictor for TCPpop for Techniques I and II. Technique III was sensitive for geometrical uncertainties, reducing TCPpop by 0.8 to 2.4% compared to planning. NTCPpop was reduced for Technique III by a factor 2.6 compared to Technique I. For all plans, the planning NTCP was strongly correlated with NTCPpop. CONCLUSIONS: Dose distributions created with Techniques I and II are insensitive for geometrical uncertainties, while Technique III resulted in a reduction of TCPpop. This reduction can be compensated by a small dose escalation, while still resulting in an NTCPpop of the rectal wall that is lower or comparable to Technique I.

Dose heterogeneity in the target volume and intensity-modulated radiotherapy to escalate the dose in the treatment of non-small-cell lung cancer.

PURPOSE: To quantify the dose escalation achievable in the treatment of non-small-cell lung cancer (NSCLC) by allowing dose heterogeneity in the target volume or using intensity-modulated radiotherapy (IMRT), or both. METHODS AND MATERIALS: Computed tomography data and contours of 10 NSCLC patients with limited movements of the tumor and representing a broad spectrum of clinical cases were selected for this study. Four irradiation techniques were compared: two conformal (CRT) and two IMRT techniques, either prescribing a homogeneous dose in the planning target volume (PTV) (CRT(hom) and IMRT(hom)) or allowing dose heterogeneity (CRT(inhom) and IMRT(inhom)). The dose heterogeneity was allowed only toward high doses, i.e., the minimum dose in the target for CRT(inhom) and IMRT(inhom) could not be lower than for the corresponding homogeneous plan. The dose in the PTV was escalated (fraction size of 2.25 Gy) until either an organ at risk reached the maximum allowed dose or the mean PTV dose reached a maximum level set at 101.25 Gy. RESULTS: When small and convex tumors were irradiated, CRT(hom) could achieve the maximum dose of 101.25 Gy, whereas for bigger and/or concave PTVs the dose level achievable with CRT(hom) was significantly lower, in 1 case even below 60 Gy. The CRT(inhom) allowed on average a 6% dose escalation with respect to CRT(hom). The IMRT(hom) achieved in all except 1 case a mean PTV dose of at least 75 Gy. The gain in mean PTV dose of IMRT(hom) with respect to CRT(hom) ranged from 7.7 to 14.8 Gy and the IMRT(hom) plans were always more conformal than the corresponding CRT(hom) plans. The IMRT(inhom) provided an additional advantage over IMRT(hom) of at least 5 Gy. For all CRT plans the achievable dose was determined by the lung dose threshold, whereas for more than half of the IMRT plans the esophagus was the dose-limiting organ. The IMRT plans were deliverable with 10-12 segments per beam and did not produce an increase of lung volume irradiated at low doses (<20 Gy). CONCLUSIONS: The dose in NSCLC treatments can be escalated by loosening the constraints on maximum dose in the target volume or using IMRT, or both. For large and concave tumors, an average dose escalation of 6% and 17% was possible when dose heterogeneity and IMRT were applied alone. When they were combined, the average dose increase was as high as 35%. Intensity-modulated RT delivered in a static mode can produce homogeneous dose distributions in the target and does not lead to an increase of lung volume receiving (very) low doses, even down to 5 Gy.

Sensitivity of treatment plan optimisation for prostate cancer using the equivalent uniform dose (EUD) with respect to the rectal wall volume parameter.

BACKGROUND AND PURPOSE: To analyse the sensitivity of plan optimisation of prostate cancer treatments with respect to changes in the volume parameter (n), when the EUD is used to control the dose in the rectal wall. PATIENTS AND METHODS: A series of plans was defined, by varying n over a range between 0.08 and 1, and testing different cost functions and beam arrangements. In all cases, the aim was to minimise the EUD in the rectal wall, while ensuring specific dose coverage of the PTV, and limiting the dose in the other OARs. The results were evaluated in terms of 3-D dose distribution and with respect to the current clinical knowledge about late rectal toxicity after irradiation. RESULTS: Different values of n lead to very similar dose distributions over the PTV (differences in mean dose < 1 Gy, differences in dose given to 99% of the volume < 1%). For the rectal wall, the following observations were made: (a) all cumulative DVH curves crossed each other around 60 Gy; (b) the rectal wall volume receiving doses between 30 and 45 Gy could change by 45 and 30%, respectively, depending on the value of n; (c) for doses higher than 70Gy the differences were typically within 5%. Different values of n also affected the position of isodose surfaces. The distance between the 70 and the 30 Gy isodose curves changed in the AP direction by a factor of 3 when n decreased from 1 to 0.08. High values of n were associated with less dose conformity and a larger volume (at least 20%) of normal tissues receiving 50 Gy or more. All DVHs for the rectal wall were below published dose toxicity thresholds except when the prescribed dose was escalated up to 86 Gy. CONCLUSIONS: In most cases, the solutions associated with n values up to 0.25 produced similar dose distribution in the rectal wall for doses above 45 Gy, complying with the dose-toxicity thresholds we analysed. The choice of a specific value of n in the optimisation requires an analysis of its effects on the dose distribution for the rectal wall, but also on other aspects, such as the value of the dose to the non-involved normal tissues.

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer.

PURPOSE: To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights. METHODS: Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan. RESULTS: For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments. CONCLUSION: Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.

A comparison of forward and inverse treatment planning for intensity-modulated radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. RESULTS: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. CONCLUSION: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance.

Importance of accurate dose calculations outside segment edges in intensity modulated radiotherapy treatment planning.

BACKGROUND AND PURPOSE: To assess the effect of differences in the calculation of the dose outside segment edges on the overall dose distribution and the optimisation process of intensity modulated radiation therapy (IMRT) treatment plans. PATIENTS AND METHODS: Accuracy of dose calculations of two treatment planning systems (TPS1 and TPS2) was assessed, to ensure that they are both suitable for IMRT treatment planning according to published guidelines. Successively, 10 treatment plans for patients with prostate and head and neck tumours were calculated in both systems. The calculations were compared in selected points as well as in combination with volumetric parameters concerning the planning target volume (PTV) and organs at risk. RESULTS: For both planning systems, the calculations agree within 2.0% or 3 mm with the measurements in the high-dose region for single and multiple segment dose distributions. The accuracy of the dose calculation is within the tolerances proposed by recent recommendations. Below 35% of the prescribed dose, TPS1 overestimates and TPS2 underestimates the measured dose values, TPS2 being closer to the experimental data. The differences between TPS1 and TPS2 in the calculation of the dose outside segments explain the differences (up to 50% of the local value) found in point dose comparisons. For the prostate plans, the discrepancies between the TPS do not translate into differences in PTV coverage, normal tissue complication probability (NTCP) values and results of the plan optimisation process. The dose-volume histograms (DVH) of the rectal wall differ below 60 Gy, thus affecting the plan optimisation if a cost function would operate in this dose region. For the head and neck cases, the two systems give different evaluations of the DVH points for the PTV (up to 22% differences in target coverage) and the parotid mean dose (1.0-3.0 Gy). Also the results of the optimisation are influenced by the choice of the dose calculation algorithm. CONCLUSIONS: In IMRT, the accuracy of the dose calculation outside segment edges is important for the determination of the dose to both organs at risks and target volumes and for a correct outcome of the optimisation process. This aspect should therefore be of major concern in the commissioning of a TPS intended for use in IMRT. Fulfilment of the accuracy criteria valid for conformal radiotherapy is not sufficient. Three-dimensional evaluation of the dose distribution is needed in order to assess the impact of dose calculation accuracy outside the segment edges on the total dose delivered to patients treated with IMRT.

Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue.

BACKGROUND AND PURPOSE: The low density of lung tissue causes a reduced attenuation of photons and an increased range of secondary electrons, which is inaccurately predicted by the algorithms incorporated in some commonly available treatment planning systems (TPSs). This study evaluates the differences in dose in normal lung tissue computed using a simple and a more correct algorithm. We also studied the consequences of these differences on the dose-effect relations for radiation-induced lung injury. MATERIALS AND METHODS: The treatment plans of 68 lung cancer patients initially produced in a TPS using a calculation model that incorporates the equivalent-path length (EPL) inhomogeneity-correction algorithm, were recalculated in a TPS with the convolution-superposition (CS) algorithm. The higher accuracy of the CS algorithm is well-established. Dose distributions in lung were compared using isodoses, dose-volume histograms (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy (V20). Published dose-effect relations for local perfusion changes and radiation pneumonitis were re-evaluated. RESULTS: Evaluation of isodoses showed a consistent overestimation of the dose at the lung/tumor boundary by the EPL algorithm of about 10%. This overprediction of dose was also reflected in a consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/-1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both parameters, a strong correlation was found between the EPL and CS algorithms yielding a straightforward conversion procedure. Re-evaluation of the dose-effect relations showed that lung complications occur at a 12-14% lower dose. The values of the TD(50) parameter for local perfusion reduction and radiation pneumonitis changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively. CONCLUSIONS: A simple tissue inhomogeneity-correction algorithm like the EPL overestimates the dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20) computed using both algorithms are strongly correlated making an easy conversion feasible. Dose-effect relations should be refitted when more accurate dose data is available.

Intensity modulated versus non-intensity modulated radiotherapy in the treatment of the left breast and upper internal mammary lymph node chain: a comparative planning study.

BACKGROUND AND PURPOSE: To compare and evaluate intensity modulated (IMRT) and non-intensity modulated radiotherapy techniques in the treatment of the left breast and upper internal mammary lymph node chain. MATERIALS AND METHODS: The breast, upper internal mammary chain (IMC), heart and lungs were delineated on a computed tomography (CT)-scan for 12 patients. Three different treatment plans were created: (1) tangential photon fields with oblique IMC electron-photon fields with manually optimized beam weights and wedges, (2) wide split tangential photon fields with a heart block and computer optimized wedge angles, and (3) IMRT tangential photon fields. For the IMRT technique, an inverse planning program (KonRad) generated the intensity profiles and a clinical three-dimensional treatment planning system (U-MPlan) optimized the segment weights. U-MPlan calculated the dose distribution for all three techniques. The normal tissue complication probabilities (NTCPs) for the organs at risk (ORs) were calculated for comparison. RESULTS: The average root mean square deviation of the differential dose-volume histogram of the breast planning target volume was 4.6, 3.9 and 3.5% and the average mean dose to the IMC was 97.2, 108.0 and 99.6% for the oblique electron, wide split tangent and IMRT techniques, respectively. The average NTCP for the ORs (i.e. heart and lungs) were comparable between the oblique electron and IMRT techniques (or=2%) for the ORs. CONCLUSIONS: The lowest NTCP values were found with the oblique electron and the IMRT techniques. The IMRT technique had the best breast and IMC target coverage.

Reduction of rectal dose by integration of the boost in the large-field treatment plan for prostate irradiation.

PURPOSE: To reduce the dose in the rectal wall from prostate irradiation at high dose levels. METHODS AND MATERIALS: Treatment plans in which the boost fields were integrated into the large fields (simultaneous integrated boost [SIB]) were compared with plans in which the large fields and boost fields were planned individually and applied in a sequential manner (sequential boost). Two target volumes were delineated: PTV1, the target volume of the large fields that is irradiated to 68 Gy, and PTV2, the target volume of the boost fields that is irradiated to 10 Gy. The sequential boost and the SIB were normalized to the mean dose in PTV2, being 78 Gy. We used a five-field intensity-modulated radiotherapy (IMRT) technique, applied in a step and shoot mode, and included beam weight optimization. A set of 5 patients with varying degree of overlap between PTV1 and the rectal wall was used for analysis. RESULTS: The SIB resulted in a reduction of the dose in the rectal wall. Rectal normal tissue complication probability (NTCP) decreased for the SIB, on average, by a factor of almost 2, compared with the sequential boost. CONCLUSION: The SIB reduced the dose in the rectal wall, compared with the sequential boost technique.