Uncomplicated Tumor Control Research Articles

SU-E-T-277: Modeling Normal Tissue Complication Probability Based On Compiled Clinical Data From Skin Cancer Radiotherapy

Purpose: Our objective is to model normal tissue complication probability (NTCP) based on published clinical data of head/face non‐melanoma skin cancers to determine optimum treatment schemes using advanced radiotherapy (RT) technologies. Methods: Reports citing crude estimates of erythema, desquamation and telangiectasia for primary basal and squamous cell carcinoma (BCC & SCC, resp) of the head/face were used in model development. The models had the form: NTCP = 1/(1+exp(‐(BED + BEDprolif x T — TD50)/k), where BED is the LQ model based biological effective dose. Uncomplicated tumor control functions (UCTCs) were created using NTCP models together with our own separately published TCP models. Values of BED maximizing UCTC were calculated and compared with 5 × 7.2 Gy in one week and 15 × 3 Gy in 3 weeks treatment schedules (BED 14 = 54.5 & 54.6 Gy, respectively). Results: Literature search yield six reports useful in the development of a TCP model for BCC/SCC. The reported a median total dose of 39.0 Gy (range: 23.9–52.4 Gy), dose per fraction of 3.3 Gy/fx (range: 1.7–7.3 Gy/fx), & total treatment time of 28.7 days (range: 12–40 days). Three NTCP and 12 UTCP models were generated for treatments with tumors of size 2cm. Maximum UCTC occurred at biological effective doses (BEDs) ranging from 36.25–52.25 Gy to the BCC/SCC tumors 2 cm in size. Conclusion: Three NTCP models for endpoints observed in skin cancer RT were developed based on published data, which can depend on the size of irradiated skin area (future work will explore the area–NTCP relationship further). BED values for single and multiple fraction treatments were identified to maximize UCTC for tumors > 2 cm in size, though smaller tumors may benefit from treatment schedules with lower BED.

Hypoxia-targeted radiotherapy dose painting for head and neck cancer using 18F-FMISO PET: A biological modeling study

Background. This study investigates the use of 18F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC). Material and methods. The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP). Results. The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138). Conclusion. Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.

Forward versus inverse planning in oropharyngeal cancer: A comparative study using physical and biological indices

Possible benefits of inverse planning. To analyze possible benefits of inverse planning intensity modulated radiation therapy (IMRT) over field-in-field 3D conformal radiation therapy (FIF-3DCRT) and to evaluate the differences if any, between low (6 Million Volts) and high energy (15 Million Volts) IMRT plans. Ten patients with squamous cell carcinoma of oropharynx, previously treated with 6 MV step and shoot IMRT were studied. V100, V33, V66 , mean dose and normal tissue complication probabilities (NTCP) were evaluated for parotid glands. Maximum dose and NTCP were the parameters for spinal cord. A two-tailed t-test was applied to analyze statistical significance between the different techniques. For combined parotid gland, a reduction of 4.374 Gy, 9.343 Gy and 7.883 Gy were achieved for D100, D66 and D33, respectively in 6 MV-IMRT when compared with FIF-3DCRT. Spinal cord sparing was better in 6 MV-IMRT (40.963 ± 2.650), with an average reduction of maximum spinal cord dose by 7.355 Gy from that using the FIF-3DCRT technique. The uncomplicated tumor control probabilities values were higher in IMRT plans thus leading to a possibility of dose escalation. Though low-energy IMRT is the preferred choice for treatment of oropharyngeal cancers, FIF-3DCRT must be given due consideration as a second choice for its well established advantages over traditional conventioan technique.

Uncomplicated Tumour Control Probability (UTCP) in post-operative radiotherapy of left breast cancer- three dimensional conformal versus Intensity Modulated Radiation Therapy (IMRT )

Uncomplicated Tumour Control Probability (UTCP) in post-operative radiotherapy of left breast cancer- three dimensional conformal versus Intensity Modulated Radiation Therapy (IMRT )

“SABER”: A new software tool for radiotherapy treatment plan evaluation

Both spatial and biological information are necessary in order to perform true optimization of a treatment plan and for predicting clinical outcome. The goal of this work is to develop an enhanced treatment plan evaluation tool which incorporates biological parameters and retains spatial dose information. A software system is developed which provides biological plan evaluation with a novel combination of features. It incorporates hyper-radiosensitivity using the induced-repair model and applies the new concept of dose convolution filter (DCF) to simulate dose wash-out effects due to cell migration, bystander effect, and/or tissue motion during treatment. Further, the concept of spatial DVH (sDVH) is introduced to evaluate and potentially optimize the spatial dose distribution in the target volume. Finally, generalized equivalent uniform dose is derived from both the physical dose distribution (gEUD) and the distribution of equivalent dose in 2 Gy fractions (gEUD2) and the software provides three separate models for calculation of tumor control probability (TCP), normal tissue complication probability (NTCP), and probability of uncomplicated tumor control (P+). TCP, NTCP, and P+ are provided as a function of prescribed dose and multivariable TCP, NTCP, and P+ plots are provided to illustrate the dependence on individual parameters used to calculate these quantities. Ten plans from two clinical treatment sites are selected to test the three calculation models provided by this software. By retaining both spatial and biological information about the dose distribution, the software is able to distinguish features of radiotherapy treatment plans not discernible using commercial systems. Plans that have similar DVHs may have different spatial and biological characteristics and the application of novel tools such as sDVH and DCF within the software may substantially change the apparent plan quality or predicted plan metrics such as TCP and NTCP. For the cases examined, both the calculation method and the application of DCF can change the ranking order of competing plans. The voxel-by-voxel TCP model makes it feasible to incorporate spatial variations of clonogen densities (n), radiosensitivities (SF2), and fractionation sensitivities (alpha/beta) as those data become available. The new software incorporates both spatial and biological information into the treatment planning process. The application of multiple methods for the incorporation of biological and spatial information has demonstrated that the order of application of biological models can change the order of plan ranking. Thus, the results of plan evaluation and optimization are dependent not only on the models used but also on the order in which they are applied. This software can help the planner choose more biologically optimal treatment plans and potentially predict treatment outcome more accurately.

Radiotherapy for hepatocellular carcinoma: Systematic review of radiobiology and modeling projections indicate reconsideration of its use

External beam radiotherapy currently has a limited role in the treatment of hepatocellular carcinoma (HCC). The purpose of this article was to review available radiobiological data on HCC and normal liver and incorporate these data into radiobiological models that may be used to explain and improve treatment. Volume doubling times of HCC were described and used to demonstrate growth of HCC with time, assuming both exponential and logistic growth. Radiosensitivity of HCC was described and used to demonstrate the probability of uncomplicated tumor control as tumor size increases. The relationship between tolerance of liver to irradiation and volume irradiated was examined. The median volume doubling time for untreated HCC was 130 days. HCC have a long period of subclinical growth. Radiosensitivity of HCC lies within the range of other tumors commonly treated with radiotherapy. When treating small volumes of normal liver, relatively high doses may be used with low risk of late radiation damage. There is a high probability of sterilizing subclinical disease and small HCC with tolerable radiation doses. New radiobiological data, modeling, emerging clinical data and the advantages offered by standard external beam radiotherapy techniques suggest the need for reconsidering the use of radiotherapy and for new trials.

Use of Normal Tissue Complication Probability Models in the Clinic

The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included.

SORS: A New Software for the Simulation of Radiotherapy Schedule

We present a software for choosing the best radiotherapy treatment schedule for head and neck cancers as a beginning radiotherapy plan or a temporarily interrupted plan. Its application occurs according to two modalities: the first adopts the best estimates for model parameters; the second takes into account the parameters' uncertainty too. In both cases, the choice becomes the schedule with the highest uncomplicated tumor control probability (UTCP). In the UTCP valuation, the normal tissue complication probability (NTCP) of each organ is related to the gravity of its possible late injury. For NTCP calculation, it has been adopted the empirical LKB (Lyman-Kutcher-Burman) model corrected for dose/fraction via linear-quadratic model and the incomplete repair effect. The tumor control probability (TCP) model is Poisson based and contains corrections for dose/fraction and regrowth effect; optionally, it can be accounted for the incomplete repair effect as well. At the end of processing, a detailed file with all informations about UTCP, TCP and single organ NTCP is furnished for every examined schedule. Moreover, a useful 3-D graphic representation of the schedule's UTCP is available, allowing the physician to easily understand the schedules with the highest radiotherapeutic efficacy. The open source characteristic allows the program to adapt to the individual clinical case as well as to be a valid support in radiobiological research.

SU-FF-T-523: A Comparison of Head and Neck IMRT Plans Optimized with Biologically Based Versus Dose-Volume Based Objectives in a Commercial Treatment Planning System

Purpose: To compare the quality of IMRT plans optimized with biologically (EUD) based versus dose-volume based objectives in a commercial treatment planning system in the treatment of head and neck cancers. Method and Materials: EUD-based optimization was utilized in the Philips Pinnacle P3 IMRT treatment planning system (licensed for Biological Evaluation) to obtain intensity-modulated radiation therapy plans for five head and neck cancer patients. These plans were evaluated against IMRT plans optimized with conventional dose-volume objectives. Each patient had twenty-six organs-at-risk (OAR) contoured within the head and neck region. The plans were compared by examining dose-volume histograms, dosimetric indices and biological endpoints. Dosimetric indices included mean, minimum and maximum doses, as well as target conformality, dose uniformity and the generalized EUD. Biological endpoints included tumor control probability (TCP), normal tissue complication probability (NTCP) and uncomplicated tumor control probability (P+). Results: Preliminary results show that the EUD-based optimization in P3 IMRT is capable of improving the sparing of OAR while maintaining target coverage. The biologically-based optimization resulted in greater dose inhomogeneity and less conformality than the dose-volume based optimization plans. It was also shown that plans optimized with EUD-based objectives could obtain similar target coverage as the dose-volume optimized plans but with fewer parameters. Conclusion: The P3 IMRT biologically-based optimization of head and neck IMRT plans resulted in equivalent target coverage while increasing the sparing of normal tissues compared to dose-volume based optimization. This system can increase the efficiency of obtaining plans of equivalent or better quality by utilizing fewer parameters and has the potential of being incorporated into routine clinical use.

SU-GG-T-411: Impact of Respiratory Gating Using 4DCT On TCP, NTCP, TI, and UTCP in Patients with Thoracic Malignancies

Objective: To evaluate the tumor control probability (TCP), normal tissue complication probability (NTCP), therapeutic index (TI) and uncomplicated tumor control probability (UTCP) from the Dosimetry of 4DCT gated treatment plans as compared to traditional non‐gated treatment plans. Method and Materials: Ten patients underwent treatment planning. Gated CTimages were obtained at full inspiration, full expiration and at 25th, 50th and 75th percentile of respiration. For non‐gated plans, planning target volume (PTV) included an all around 1 cm margin for tumor motion and 0.5 cm for set‐up error. For gated plans, tumor volumes of individual CTimages were superimposed with a 0.5 cm margin for set‐up error. The prescription dose was 60–70 Gy with 2 Gy per fraction. Dose Volume Histograms were generated for PTV and normal tissues in each treatment plan. Gated and non‐gated plans were compared based on TCP, NTCP, TI and UTCP. Results: TCP was higher for gated plans irrespective of α/β = 5 or 10. Specifically, for α/β = 5, SF2 = 0.4, TCP was 99.44% and 90.21% for gated versus 94.48% and 67.82%, for non gated plans with CCD of 10M and 220 M, respectively. NTCPs for lung, esophagus, heart and spinal cord were 7.96%, 5.23%, 1.66% and 0.38% with gating versus 26%, 8.25%, 9.36% and 0.52% without gating. Gated plans resulted in higher TIs for lung, esophagus, heart, and spinal cord by a factor > 3.4, 1.6, 5.9, and 1.4 respectively. The differences in UTCPs between gated and non gated plans were greater than 27% irrespective of α/β and CCD, for SF2 of 0.1 to 0.4. Conclusion: 4DCT respiratory gating allows reduced radiation field with lower doses to normal tissue and hence higher therapeutic gain.

TH‐C‐224C‐06: Using Quality of Life Information to Rationally Incorporate Normal Tissue Effects Into Treatment Plan Evaluation and Scoring

Purpose: Modern radiotherapy treatment planning systems provide an increasing number of competing plans. The decision to select a particular plan for treatment is generally made by a radiation oncologist based on training and clinical experience. The criteria applied are often poorly‐defined, qualitative, and largely based on tradition and familiarity. A “realistic” approach utilizing decision analysis tools to evaluate/rank treatment plans based on quality adjusted life years (QALY) expectancy was developed. Method and Materials: The decision analysis methods were applied to the concept of uncomplicated tumor control probability (UTCP). The expected outcome for an anticipated course of radiation was described as a series of probabilities: alive, free of disease without complication; alive with disease; alive with complication, etc. For each of these states of health, a utility can be assigned based on published work or empirical estimates. The total QALY' for a particular treatment plan represent the product of duration‐weighted states of health. The formalism for UTCP was generalized to incorporate the total QALY (UTCPQALY) for a particular treatment. Results: This approach was applied to compare the clinical treatment plans of 200 patients who received high‐dose external‐beam for unresectable non‐small cell lung cancer. Thirty nine out of the 200 patients developed radiation‐induced pneumonitis with the grade distribution of 8.7%, 69.6%, and 21.7% for grades 1, 2, and 3, respectively. The plan ranking based on the traditional UTCP and pneumonitis QALY‐weighted UTCP (UTCPQALY) values were different. The UTCP varied significantly, reaching values of 0.5. Using UTCPQALY scoring, the mild complications importance is downplayed compared to the severe complications, with all UTCPQALY values above 0.85. The QALY‐weighted UTCP's appear to provide better clinical realistic differentiator between plans. Conclusion: The construct presented represents a potential improvement in the current methods used to compare plans. Formulas presented can be readily incorporated into planning systems.

Damage assessment in gastric cancer treatment with adjuvant radiochemotherapy: calculation of the NTCP’s from the differential HDV of the organs at risk

To calculate the Normal Tissue Complication Probabilities (NTCP) for the liver, right kidney, left kidney and spinal cord, as well as the global Uncomplicated Tumour Control Probability (UTCP) in gastric cancer patients who underwent a treatment with radiotherapy after radical surgery in our environment. In April 2000, a postoperative chemotherapy (QT-RT) protocol started in the province of Malaga for Gastric Adenocarcinomas with postsurgical stage II or higher (pT3-4 and/or pN+). This clinical protocol served as a base for our NTCP and UTCP retrospective theorical study. A virtual simulation and a 3D planning were made in all cases. The differential HDV, selected for each patient were obtained for the 4 organs at risk (OR). Hystograms reduction was made by the Kutcher and Burman's Effective Volume method. NTCP calculations by Lyman's models. The following variables were calculated: maximal dose for each organ (Dmax), Effective Volume (Veff), TD50 (Veff/Vref); NTCP for each organ of the patient; global UTCP for each patient. Differences between the 2 treatment techniques were analysed (2-field versus 4-field technique). For the NTCP calculations the computer application Albireo 1.0(R) was used. 29 patients to assess with an average age of 54 +/- 10 years (range: 38-71); 65.5% men/34.5% women. The technique used was the field technique AP-PA in the 51.7% (15) and with 4 fields in 48.3% (14) of the cases. The global damage is estimated in 16% with a range between 0 and 37%. This goes up to 25% with the 2-field technique, with a wide range between 2 and 48% and it remains reduced to 4%, within a range between 0 and 12% when 4 fields are used. There were significant differences concerning the estimated damage probability (NTCP) on liver, spinal cord and left kidney, depending on the use of two or four fields. NTCP and the global UTCP values of the organs at risk allow to compare a technique net benefit from another in each particular case, although in our theoretical study the comparison was done among the patients. It is important to stress that the calculations of the TCP and NTCP have a limited quantitative signification but they are useful and beneficial in order to decide between treatment plans when they are supported by the clinical knowledge.

An assessment of Biologically-based Optimization (BORT) in the IMRT era

The purpose of this study was to investigate the role of biological-based IMRT (BORT) in treatment planning development; more specifically, to assess the possible advantages of BORT over the classic 3-dimensional conformal radiation therapy (3DRT) and dose-based IMRT based on quantitative and qualitative indices. Three clinical cases are presented to evaluate the differences of BORT, IMRT, and 3DRT. 3DRT, IMRT, and BORT plans were generated for each case using a commercially available treatment planning system (Pinnacle by Philips). The plans were compared by evaluating biological endpoints such as tumor control probability (TCP), normal tissue control probability (NTCP), and uncomplicated tumor control probability (P+), as well as isodose line distribution, dose-volume histograms (DVHs), and dose uniformity. In all cases of this study, BORT yielded improved isodose coverage and P+. Our preliminary results suggest that BORT could play an important role in treatment planning optimization, especially as biological models and predictive assays become more accurate. Further case studies are needed to establish a definitive role for this type of optimization.

A unifying framework for multi-criteria fluence map optimization models

Models for finding treatment plans for intensity modulated radiation therapy are usually based on a number of structure-based treatment plan evaluation criteria, which are often conflicting. Rather than formulating a model that a priori quantifies the trade-offs between these criteria, we consider a multi-criteria optimization approach that aims at finding the so-called undominated treatment plans. We present a unifying framework for studying multi-criteria optimization problems for treatment planning that establishes conditions under which treatment plan evaluation criteria can be transformed into convex criteria while preserving the set of undominated treatment plans. Such transformations are identified for many of the criteria that have been proposed to date, establishing equivalences between these criteria. In addition, it is shown that the use of a nonconvex criterion can often be avoided by transformation to an equivalent convex criterion. In particular, we show that models employing criteria such as tumour control probability, normal tissue complication probability, probability of uncomplicated tumour control, as well as sigmoidal transformations of (generalized) equivalent uniform dose are equivalent to models formulated in terms of separable voxel-based criteria that penalize dose in individual voxels.

Modeling the impact of treatment uncertainties in radiotherapy

The aim of this thesis is to model the impact (dosimetric and radiobiological) of prostate radiotherapy treatment uncertainties and techniques for displaying potential dose errors. A Monte Carlo code is written to simulate both the treatment planning and delivery phases. Distributions of systematic organ motion, systematic positioning error, random organ motion, random positioning error, and interpatient cell sensitivity are taken from the literature. These distributions are used to sample the position and size of the prostate and rectum at each fraction of treatment. Dose to organ voxels are assigned from precalculated dose distributions (four‐field box using 6 MV photons with margins around the clinical target volume of 0.5, 1.0, and 1.5 cm). In particular, the poor estimation of prostate mean position from one planning CT series is investigated and shown to introduce large dose uncertainty. A convolution kernel is suggested that considers multiple pre‐treatment CT scans to better estimate mean prostate position. The radiobiological impact of the treatment uncertainties is evaluated in terms of tumor control probability for prostate, normal tissue complication probability for rectal bleeding and uncomplicated tumor control probability using established models. Local prostate control is highly sensitive to treatment uncertainties with inadequate margin size and to interpatient radiosensitivity. Rectal bleeding is more sensitive to margin size than to deformation. A number of ways to display the dosimetric uncertainty are presented. The display tools proposed allow the planner to consider potential variations in dose visually and may assist with margin size considerations.

The role Of intensity-modulated radiotherapy in the treatment of parotid tumors

Purpose: To compare intensity-modulated radiotherapy (IMRT) treatment plans with three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the suitability of IMRT for the treatment of tumors of the parotid gland. Methods and Materials: One 3D-CRT treatment plan and 10 IMRT treatment plans with differing beam arrangements were produced for each of nine patient data sets. The plans were compared using regret analysis, dose conformity, dose to organs at risk, and uncomplicated tumor control probability (UTCP). Results: The target dose was comparable in the 3D-CRT and IMRT plans, although improvements were seen when seven and nine IMRT fields were used. IMRT reduced the mean dose to the contralateral parotid gland and the maximum doses to the brain and the spinal cord, but increased the ipsilateral lens dose in some cases. Each IMRT arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute difference was 9.6%. Conclusions: IMRT is a suitable means for treating cancer of the parotid, and a five-field class solution is proposed. It produced substantial sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose escalation.

Radiothérapie conformationnelle : la tomothérapie

Conformal radiation therapy allows the possibility of delivering high doses at the tumor volume whilst limiting the dose to the surrounding tissues and diminishing the secondary effects. With the example of the conformal radiation therapy used at the AZ VUB (3DCRT and tomotherapy), two treatment plans of a left ethmoid carcinoma will be evaluated and discussed in detail. The treatment of ethmoid cancer is technically difficult for both radiation therapy and surgery because of the anatomic constraints and patterns of local spread. A radiation therapy is scheduled to be delivered after surgical resection of the tumor. The treatment plan for the radiation therapy was calculated on a three-dimensional (3D) treatment planning system based on virtual simulation with a beam’s eye view: George Sherouse’s Gratis®. An effort was made to make the plan as conformal and as homogeneous as possible to deliver a dose of 66 Gy in 33 fractions at the tumor bed with a maximum dose of 56 Gy to the right optic nerve and the chiasma. To establish the clinical utility and potential advantages of tomotherapy over 3DCRT for ethmoid carcinoma, the treatment of this patient was also planned with Peacock Plan®. For both treatment plans the isodose distributions and cumulative dose volume histograms (CDVH) were computed. Superimposing the CDVHs yielded similar curves for the target and an obvious improvement for organs at risk such as the chiasma, brainstem and the left eye when applying tomotherapy. These results have also been reflected in the tumor control probabilities (equal for both plans) and the normal tissue complication probabilities (NTCP), yielding significant reductions in NTCP for tomotherapy. The probability of uncomplicated tumor control was 52.7% for tomotherapy against 38.3% for 3DCRT.

Conformal irradiation of concave-shaped PTVs in the treatment of prostate cancer by simple 1D intensity-modulated beams

Background: In the case of concave-shaped PTVs including prostate (P) and seminal vesicles (SV), intensity-modulated radiation therapy (IMRT) should improve the therapeutic ratio of the treatment of prostate cancer. Purpose: Comparing IMRT by simple 1D modulations with conventional 3D conformal therapy (i.e. non-IMRT) in the treatment of concave-shaped PTVs including P+SV. Materials and methods: For five patients having a concave-shaped PTV (P+SV) previously treated at our Institute with conformal radiotherapy, conventional 3- and 4-fields conformal plans were compared with IMRT plans in terms of biological indices. IMRT plans were generated by using five equi-spaced beams with a partial shielding of the rectum obtainable with our single-absorber modulation technique (Fiorino C, Lev A, Fusca M, Cattaneo GM, Rudello F, Calandrino R. Dynamic beam modulation by using a single dynamic absorber. Phys. Med. Biol. 1995;40:221–240). The modulation was one-dimensional and the shape of the beams was at single minimum in correspondence with the ‘core’ of the rectum; the beam intensity in the minimum was set equal to 20 or 40% of the open beam intensity. All plans were simulated on the CADPLAN TPS using a pencil-beam based algorithm (with 18 MV X-rays). Tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) (for rectum, bladder and femoral head) were calculated for all situations when varying the isocentre dose from 60 to 90 Gy. Dose distributions were corrected taking dose fractionation into account through the linear-quadratic model; for the TCP/NTCP estimations the Webb–Nahum and the Lyman–Kutcher models were respectively applied. Three different scores were considered: (a) increase of TCP while keeping rectum NTCP equal to 5% (TCP(5%)); (b) increase of the uncomplicated tumour control probability (P+); (c) increase of the biological-based scoring function (S+), developed by Mohan et al. (Mohan R, Mageras GS, Baldwin B, Clinically relevant optimization of 3D conformal treatments. Med. Phys. 1992;19:933–944). The impact of the uncertainty in the knowledge of the parameters of the biological models was investigated for TCP(5%). Results: (a) The average gain in TCP(5%) when considering IMRT against non-IMRT conformal plans was 7.3% (range 5.0–13.5%); (b) the average increase of P+ was 3.4% (range: 1.0–8.5%); and (c) the average increase of S+ was 5.4% (range 2.9–12.4%). The largest gain was found for one patient (patient 5) showing a significantly larger overlapping between PTV and rectum. Conclusions: Simple 1D-IMRT may clearly improve the therapeutic ratio in the treatment of concave-shaped PTVs including P and SV. In the range of clinically suitable values, the impact of the uncertainty of the parameters n and σ α does not significantly alter the main results concerning the gain in TCP(5%). The reported gain in terms of P+ and S+ should be considered with great caution because of the intrinsic uncertainties of the model's parameters and, for bladder, because the ‘true’ DVH (considering variations of the shape and dimension due to variable filling) may be very different from the DVH calculated on a single CT scan. Further investigations should consider inversely-optimised 1D and 2D-IMRT plan in order to compare them in terms of cost-benefit.

Vergleich verschiedener Optimierungskonzepte für die intensitätsmodulierte Strahlentherapie

Intensity modulated irradiation beams provide a substantial progress for radiotherapy. Both, the conformity of the dose distribution with the target volume and sparing of organs at risk are improved. The determination of the fluence profiles is an optimization problem. It depends on the formulation of the objective function, whether a meaningful solution can be achieved. The parameters to maximize uncomplicated tumor control directly, are not yet known with sufficient accuracy. In this work, the usual method of minimizing the quadratic deviation between the calculated and desired dose distributions is compared to methods where clinically proven dose constraints are used directly. For the first approach it is necessary to adapt weighting factors interactively in order to achieve the desired result. Algorithms based on the use of dose limits are faster and allow to simulate usual clinical strategies like palliation or curative treatment very easily. The differences of the dose distributions for this strategies are described as a function of the number of beam portals.

An adaptive control algorithm for optimization of intensity modulated radiotherapy considering uncertainties in beam profiles, patient set-up and internal organ motion

A new general beam optimization algorithm for inverse treatment planning is presented. It utilizes a new formulation of the probability to achieve complication-free tumour control. The new formulation explicitly describes the dependence of the treatment outcome on the incident fluence distribution, the patient geometry, the radiobiological properties of the patient and the fractionation schedule. In order to account for both measured and non-measured positioning uncertainties, the algorithm is based on a combination of dynamic and stochastic optimization techniques. Because of the difficulty in measuring all aspects of the intra- and interfractional variations in the patient geometry, such as internal organ displacements and deformations, these uncertainties are primarily accounted for in the treatment planning process by intensity modulation using stochastic optimization. The information about the deviations from the nominal fluence profiles and the nominal position of the patient relative to the beam that is obtained by portal imaging during treatment delivery, is used in a feedback loop to automatically adjust the profiles and the location of the patient for all subsequent treatments. Based on the treatment delivered in previous fractions, the algorithm furnishes optimal corrections for the remaining dose delivery both with regard to the fluence profile and its position relative to the patient. By dynamically refining the beam configuration from fraction to fraction, the algorithm generates an optimal sequence of treatments that very effectively reduces the influence of systematic and random set-up uncertainties to minimize and almost eliminate their overall effect on the treatment. Computer simulations have shown that the present algorithm leads to a significant increase in the probability of uncomplicated tumour control compared with the simple classical approach of adding fixed set-up margins to the internal target volume.