Tumour bed delineation for partial breast/breast boost radiotherapy: what is the optimal number of implanted markers?

PURPOSE: International consensus has not been reached regarding the optimal number of implanted tumour bed (TB) markers for partial breast/breast boost radiotherapy target volume delineation. Four common methods are: insertion of 6 clips (4 radial, 1 deep and 1 superficial), 5 clips (4 radial and 1 deep), 1 clip at the chest wall, and no clips. We compared TB volumes delineated using 6, 5, 1 and 0 clips in women who have undergone wide-local excision (WLE) of breast cancer (BC) with full-thickness closure of the excision cavity, in order to determine the additional margin required for breast boost or partial breast irradiation (PBI) when fewer than 6 clips are used. METHODS: Ten patients with invasive ductal BC who had undergone WLE followed by implantation of six fiducial markers (titanium clips) each underwent CT imaging for radiotherapy planning purposes. Retrospective processing of the DICOM image datasets was performed to remove markers and associated imaging artefacts, using an in-house software algorithm. Four observers outlined TB volumes on four different datasets for each case: (1) all markers present (CT6M); (2) the superficial marker removed (CT(5M)); (3) all but the chest wall marker removed (CTCW); (4) all markers removed (CT(0M)). For each observer, the additional margin required around each of TB(0M), TBCW, and TB(5M) in order to encompass TB(6M) was calculated. The conformity level index (CLI) and differences in centre-of-mass (COM) between observers were quantified for CT(0M), CTCW, CT(5M), CT(6M). RESULTS: The overall median additional margins required to encompass TB(6M) were 8mm (range 0-28 mm) for TB(0M), 5mm (range 1-13 mm) for TBCW, and 2mm (range 0-7 mm) for TB(5M). CLI were higher for TB volumes delineated using CT(6M) (0.31) CT(5M) (0.32) than for CTCW (0.19) and CT(0M) (0.15). CONCLUSIONS: In women who have undergone WLE of breast cancer with full-thickness closure of the excision cavity and who are proceeding to PBI or breast boost RT, target volume delineation based on 0 or 1 implanted markers is not recommended as large additional margins are required to account for uncertainty over true TB location. Five implanted markers (one deep and four radial) are likely to be adequate assuming the addition of a standard 10-15 mm TB-CTV margin. Low CLI values for all TB volumes reflect the sensitivity of low volumes to small differences in delineation and are unlikely to be clinically significant for TB(5M) and TB(6M) in the context of adequate TB-CTV margins.

The use of the Active Breathing Coordinator throughout radical non-small-cell lung cancer (NSCLC) radiotherapy.

PURPOSE: To assess feasibility and reproducibility of an Active Breathing Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung cancer, and compare lung dosimetric parameters between free-breathing and ABC plans. METHODS AND MATERIALS: A total of 18 patients, recruited into an approved study, had free-breathing and ABC breath-hold treatment plans generated. Lung volume, the percentage volume of lung treated to a dose of ≥20 Gy (V(20)), and mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5 days/week) was delivered in breath-hold. Repeat breath-hold computed tomography scans were used to assess change in gross tumor volume (GTV) size and position. Setup error was also measured and potential GTV-planning target volume (PTV) margins calculated. RESULTS: Seventeen of 18 patients completed radiotherapy using ABC daily. Intrafraction tumor position was consistent, but interfraction variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions, respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction in GTV from planning to end of treatment was 25% (p = 0.003). Potentially required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions. ABC reduced V(20) by 13% (p = 0.0001), V(13) by 12% (p = 0.001), and MLD by 13% (p < 0.001) compared with free-breathing; lung volume increased by 41% (p < 0.001). CONCLUSIONS: Clinically significant movements of GTV were seen during radiotherapy for non-small-cell lung cancer using ABC. Image guidance is recommended with ABC. The use of ABC can reduce dose volume parameters determining lung toxicity, and might allow for equitoxic radiotherapy dose escalation.

A margin model to account for respiration-induced tumour motion and its variability.

In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i.e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory-specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available.

A comparison of the use of bony anatomy and internal markers for offline verification and an evaluation of the potential benefit of online and offline verification protocols for prostate radiotherapy.

PURPOSE: To evaluate the utility of intraprostatic markers in the treatment verification of prostate cancer radiotherapy. Specific aims were: to compare the effectiveness of offline correction protocols, either using gold markers or bony anatomy; to estimate the potential benefit of online correction protocol's using gold markers; to determine the presence and effect of intrafraction motion. METHODS AND MATERIALS: Thirty patients with three gold markers inserted had pretreatment and posttreatment images acquired and were treated using an offline correction protocol and gold markers. Retrospectively, an offline protocol was applied using bony anatomy and an online protocol using gold markers. RESULTS: The systematic errors were reduced from 1.3, 1.9, and 2.5 mm to 1.1, 1.1, and 1.5 mm in the right-left (RL), superoinferior (SI), and anteroposterior (AP) directions, respectively, using the offline correction protocol and gold markers instead of bony anatomy. The subsequent decrease in margins was 1.7, 3.3, and 4 mm in the RL, SI, and AP directions, respectively. An offline correction protocol combined with an online correction protocol in the first four fractions reduced random errors further to 0.9, 1.1, and 1.0 mm in the RL, SI, and AP directions, respectively. A daily online protocol reduced all errors to <1 mm. Intrafraction motion had greater impact on the effectiveness of the online protocol than the offline protocols. CONCLUSIONS: An offline protocol using gold markers is effective in reducing the systematic error. The value of online protocols is reduced by intrafraction motion.

Evaluation of two methods of predicting MLC leaf positions using EPID measurements.

In intensity modulated radiation treatments (IMRT), the position of the field edges and the modulation within the beam are often achieved with a multileaf collimator (MLC). During the MLC calibration process, due to the finite accuracy of leaf position measurements, a systematic error may be introduced to leaf positions. Thereafter leaf positions of the MLC depend on the systematic error introduced on each leaf during MLC calibration and on the accuracy of the leaf position control system (random errors). This study presents and evaluates two methods to predict the systematic errors on the leaf positions introduced during the MLC calibration. The two presented methods are based on a series of electronic portal imaging device (EPID) measurements. A comparison with film measurements showed that the EPID could be used to measure leaf positions without introducing any bias. The first method, referred to as the "central leaf method," is based on the method currently used at this center for MLC leaf calibration. It mimics the manner in which leaf calibration parameters are specified in the MLC control system and consequently is also used by other centers. The second method, a new method proposed by the authors and referred to as the "individual leaf method," involves the measurement of two positions for each leaf (-5 and +15 cm) and the interpolation and extrapolation from these two points to any other given position. The central leaf method and the individual leaf method predicted leaf positions at prescribed positions of -11, 0, 5, and 10 cm within 2.3 and 1.0 mm, respectively, with a standard deviation (SD) of 0.3 and 0.2 mm, respectively. The individual leaf method provided a better prediction of the leaf positions than the central leaf method. Reproducibility tests for leaf positions of -5 and +15 cm were performed. The reproducibility was within 0.4 mm on the same day and 0.4 mm six weeks later (1 SD). Measurements at gantry angles of 0 degrees, 90 degrees, and 270 degrees for leaf positions of -5 and +15 cm showed no significant effect of gravity. The individual leaf method could be used in various applications to improve the accuracy of radiotherapy treatment from planning to delivery. Three cases are discussed: IMRT beam verification, MLC calibration and dose calculation.

The susceptibility of IMRT dose distributions to intrafraction organ motion: an investigation into smoothing filters derived from four dimensional computed tomography data.

This study investigated the sensitivity of static planning of intensity-modulated beams (IMBs) to intrafraction deformable organ motion and assessed whether smoothing of the IMBs at the treatment-planning stage can reduce this sensitivity. The study was performed with a 4D computed tomography (CT) data set for an IMRT treatment of a patient with liver cancer. Fluence profiles obtained from inverse-planning calculations on a standard reference CT scan were redelivered on a CT scan from the 4D data set at a different part of the breathing cycle. The use of a nonrigid registration model on the 4D data set additionally enabled detailed analysis of the overall intrafraction motion effects on the IMRT delivery during free breathing. Smoothing filters were then applied to the beam profiles within the optimization process to investigate whether this could reduce the sensitivity of IMBs to intrafraction organ motion. In addition, optimal fluence profiles from calculations on each individual phase of the breathing cycle were averaged to mimic the convolution of a static dose distribution with a motion probability kernel and assess its usefulness. Results from nonrigid registrations of the CT scan data showed a maximum liver motion of 7 mm in superior-inferior direction for this patient. Dose-volume histogram (DVH) comparison indicated a systematic shift when planning treatment on a motion-frozen, standard CT scan but delivering over a full breathing cycle. The ratio of the dose to 50% of the normal liver to 50% of the planning target volume (PTV) changed up to 28% between different phases. Smoothing beam profiles with a median-window filter did not overcome the substantial shift in dose due to a difference in breathing phase between planning and delivery of treatment. Averaging of optimal beam profiles at different phases of the breathing cycle mainly resulted in an increase in dose to the organs at risk (OAR) and did not seem beneficial to compensate for organ motion compared with using a large margin. Additionally, the results emphasized the need for 4D CT scans when aiming to reduce the internal margin (IM). Using only a single planning scan introduces a systematic shift in the dose distribution during delivery. Smoothing beam profiles either based on a single scan or over the different breathing phases was not beneficial for reducing this shift.

Monte Carlo modelling of a-Si EPID response: the effect of spectral variations with field size and position.

This study focused on predicting the electronic portal imaging device (EPID) image of intensity modulated radiation treatment (IMRT) fields in the absence of attenuation material in the beam with Monte Carlo methods. As IMRT treatments consist of a series of segments of various sizes that are not always delivered on the central axis, large spectral variations may be observed between the segments. The effect of these spectral variations on the EPID response was studied with fields of various sizes and off-axis positions. A detailed description of the EPID was implemented in a Monte Carlo model. The EPID model was validated by comparing the EPID output factors for field sizes between 1 x 1 and 26 x 26 cm2 at the isocenter. The Monte Carlo simulations agreed with the measurements to within 1.5%. The Monte Carlo model succeeded in predicting the EPID response at the center of the fields of various sizes and offsets to within 1% of the measurements. Large variations (up to 29%) of the EPID response were observed between the various offsets. The EPID response increased with field size and with field offset for most cases. The Monte Carlo model was then used to predict the image of a simple test IMRT field delivered on the beam axis and with an offset. A variation of EPID response up to 28% was found between the on- and off-axis delivery. Finally, two clinical IMRT fields were simulated and compared to the measurements. For all IMRT fields, simulations and measurements agreed within 3%-0.2 cm for 98% of the pixels. The spectral variations were quantified by extracting from the spectra at the center of the fields the total photon yield (Ytotal), the photon yield below 1 MeV (Ylow), and the percentage of photons below 1 MeV (Plow). For the studied cases, a correlation was shown between the EPID response variation and Ytotal, Ylow, and Plow.

Spatial aspects of combined modality radiotherapy.

BACKGROUND AND PURPOSE: A combined modality radiotherapy (CMRT) incorporates both external beam radiotherapy (EBT) and targeted radionuclide therapy (TRT) components. The spatial aspects of this combination were explored by utilising intensity modulated radiotherapy (IMRT) to provide a non-uniform EBT dose distribution. PATIENTS AND METHODS: Three methods of prescribing the required non-uniform distribution of EBT dose are described, based on both physical and biological criteria according to the distribution of TRT uptake. The results and consequences of these prescriptions are explored by application to three examples of patient data. RESULTS: The planning procedure adopted allowed IMRT plans to be produced that met the prescription requirements. However, when the treatment was planned as a CMRT, compared with the use of EBT alone, more satisfactory target doses could be achieved with lower doses to normal tissues. The effects of errors in EBT delivery and in the functional data were found to cause a non-uniform prescription to tend towards the uniform case. CONCLUSIONS: The methods and results are relevant for more general biological treatment planning, in which IMRT may be used to produce dose distributions prescribed according to tumour function. The effects of delivery and dose calculation errors can have a significant impact on how such treatments should be planned.

Patient radiation doses for electron beam CT.

A Monte Carlo based computer model has been developed for electron beam computed tomography (EBCT) to calculate organ and effective doses in a humanoid hermaphrodite phantom. The program has been validated by comparison with experimental measurements of the CT dose index in standard head and body CT dose phantoms; agreement to better than 8% has been found. The robustness of the model has been established by varying the input parameters. The amount of energy deposited at the 12:00 position of the standard body CT dose phantom is most susceptible to rotation angle, whereas that in the central region is strongly influenced by the beam quality. The program has been used to investigate the changes in organ absorbed doses arising from partial and full rotation about supine and prone subjects. Superficial organs experience the largest changes in absorbed dose with a change in subject orientation and for partial rotation. Effective doses for typical clinical scan protocols have been calculated and compared with values obtained using existing dosimetry techniques based on full rotation. Calculations which make use of Monte Carlo conversion factors for the scanner that best matches the EBCT dosimetric characteristics consistently overestimate the effective dose in supine subjects by typically 20%, and underestimate the effective dose in prone subjects by typically 13%. These factors can therefore be used to correct values obtained in this way. Empirical dosimetric techniques based on the dose-length product yield errors as great as 77%. This is due to the sensitivity of the dose length product to individual scan lengths. The magnitude of these errors is reduced if empirical dosimetric techniques based on the average absorbed dose in the irradiated volume (CTDIvol) are used. Therefore conversion factors specific to EBCT have been calculated to convert the CTDIvol to an effective dose.

Analysis of stochastic noise in intensity-modulated beams.

Inverse planning techniques are known to produce intensity-modulated beams (IMBs) that are highly modulated. They are characterized by the fact that they contain high-frequency modulations that are absent in the profiles that are easier to deliver. For the purpose of this study these clinically unwanted fluctuations are being defined as 'noise'. Although these highly modulated solutions are also optimal solutions, as soon as the profiles are being delivered, they become unfavourable with respect to delivery efficiency and the analysis and verification of treatment. The aim of this work was therefore to understand the origins of the structure and complexity of IMBs. Ultimately, if one can characterize the essential features in optimum beam profiles, it might be possible to control the frequency distribution of IMBs and simplify the IMRT planning and delivery process. The study was based on two common optimization techniques: simulated annealing (SA) and gradient-descent (GD). The assumptions made at the start of this work were that the stochastic noise caused by the SA optimization technique is dominant over other sources of noise and that it could be separated out from the essential modulation after convergence of the cost function by averaging minimum-cost fluence profiles. The results indicate that there are three possible sources of stochastic noise in IMBs, i.e. the optimization technique, the cost function and the definition of convergence of that cost function. In terms of the optimization technique itself, it was confirmed that the gradient-descent technique does not introduce stochastic noise in the IMBs. The SA technique does introduce stochastic noise but averaging of minimum-cost fluence profiles does not result in smoother beam profiles. This originates from the fact that this type of noise is not the dominant factor in the optimization, but rather the curvature of the cost function close to the global minimum. It is shown that the choice of initial temperature in the SA optimization technique is crucial for the convergence of the cost function and the frequency distribution of the fluence profiles. If the initial temperature is too small the stochastic noise will get frozen into the fluence profiles and become the dominant component of noise, resulting in very random-looking and difficult to deliver patterns.

Application of the linear-quadratic model to combined modality radiotherapy.

PURPOSE: Methods of performing dosimetry for a combined modality radiotherapy (CMRT) consisting of a targeted radionuclide therapy (TRT) and separately delivered external beam therapy (EBT) have been established using the biologically effective dose (BED). However, a concurrent delivery of the two therapies may influence the radiobiologic effect of the treatment resulting from interaction between the therapies, and this situation has been modeled to assess the likely consequences of this regime. METHODS AND MATERIALS: A general form of the linear-quadratic model with a dose protraction factor was applied to concurrent delivery of EBT and TRT. Contributions to total BED from intra- and intermodality effects were calculated, and parameter values varied to determine conditions under which the intermodality contributions were likely to be most significant. A Poisson model of tumor control probability (TCP) was used to assess the predicted effect of concurrent delivery on treatment outcome. RESULTS: In general, over a wide range of parameter values, the effect of intermodality interactions in CMRT is small, increasing total BED delivered to tumor by approximately 1%, and producing a negligible increase in TCP. Synergistic effects could be greater in normal tissues if high doses were received from both therapies, with intermodality terms increasing total BED delivered by approximately 6% in the general case, and by approximately 18% for the case of slow repair in the spinal cord. A significant synergistic effect was predicted between EBT and I-125 seed therapy of the prostate when values of alpha/beta = 1.2 Gy, alpha = 0.026 Gy, mu = 0.36 h(-1) and N(0) = 138 clonogens were used, with TCP increasing from approximately 0.5 to 0.6. CONCLUSIONS: Under most clinical conditions, the relative temporal delivery of these two therapies is unlikely to significantly influence the overall radiobiologic effect to tumor at the cellular level. Synergistic effects may, however, be more significant in normal tissues and for tumors with low values of alpha/beta and alpha.

Combinational use of conformal and intensity-modulated beams in radiotherapy planning.

Intensity-modulated (IM) beam profiles computed by inverse-planning systems tend to be complex and may have multiple spatial minima and maxima. In addition to the structure originating from the treatment objectives, beam profiles might contain stochastic structure or noise and numerical artefacts, which present certain practical difficulties. The combinational use of conformal and intensity-modulated beams could be a different method of making the total fluence distribution less noisy and deliverable without compromising the advantages of IMRT. The investigation of this possibility provided the basis for this paper. A treatment-planning study was performed to compare plans combining modulated and unmodulated beams with a 5-field, equally spaced, full IMRT plan for treating the prostate and seminal vesicles in three patients. Beam angles for this study were 0 degrees, 72 degrees, 144 degrees, 216 degrees and 288 degrees. Additionally, a study was performed on a patient with a different beam arrangement (36 degrees, 108 degrees, 180 degrees, 252 degrees, 324 degrees) from the first study to test the obtained results. This study has demonstrated that it is possible to substitute up to two conformal beams in the originally full IMRT plan when carefully selecting the conformal beam angles. Making the anterior beam (0 degrees) and an anterior oblique beam (between 0 degrees and 90 degrees) conformal leads to a reduction in the total number of monitor units and segments of about 15% and 39%, respectively. Additionally, these two open fields can be used for simpler treatment verification.