Complication-free Tumor Control Research Articles

Automated Volumetric Modulated Arc Therapy Treatment Planning for Stage III Lung Cancer: How Does It Compare With Intensity-Modulated Radio Therapy?

To compare the quality of volumetric modulated arc therapy (VMAT) or intensity-modulated radiation therapy (IMRT) plans generated by an automated inverse planning system with that of dosimetrist-generated IMRT treatment plans for patients with stage III lung cancer. Two groups of 8 patients with stage III lung cancer were randomly selected. For group 1, the dosimetrists spent their best effort in designing IMRT plans to compete with the automated inverse planning system (mdaccAutoPlan); for group 2, the dosimetrists were not in competition and spent their regular effort. Five experienced radiation oncologists independently blind-reviewed and ranked the three plans for each patient: a rank of 1 was the best and 3 was the worst. Dosimetric measures were also performed to quantitatively evaluate the three types of plans. Blind rankings from different oncologists were generally consistent. For group 1, the auto-VMAT, auto-IMRT, and manual IMRT plans received average ranks of 1.6, 2.13, and 2.18, respectively. The auto-VMAT plans in group 1 had 10% higher planning tumor volume (PTV) conformality and 24% lower esophagus V70 (the volume receiving 70 Gy or more) than the manual IMRT plans; they also resulted in more than 20% higher complication-free tumor control probability (P+) than either type of IMRT plans. The auto- and manual IMRT plans in this group yielded generally comparable dosimetric measures. For group 2, the auto-VMAT, auto-IMRT, and manual IMRT plans received average ranks of 1.55, 1.75, and 2.75, respectively. Compared to the manual IMRT plans in this group, the auto-VMAT plans and auto-IMRT plans showed, respectively, 17% and 14% higher PTV dose conformality, 8% and 17% lower mean lung dose, 17% and 26% lower mean heart dose, and 36% and 23% higher P+. mdaccAutoPlan is capable of generating high-quality VMAT and IMRT treatment plans for stage III lung cancer. Manual IMRT plans could achieve quality similar to auto-IMRT plans if best effort was spent.

SU-E-T-458: Radiobiological Comparison of Single and Dual-Isotope Prostate Seed Implants.

Several isotopes are available for low dose-rate brachytherapy of the prostate. Currently, most implants use a single isotope. However, the use of dual-isotope implants may yield an advantageous combination of characteristics such as half-life and relative biological effectiveness. However, the use of dual-isotope implants complicates treatment planning and quality assurance. Do the benefits of dual-isotope implants outweigh the added difficulty? The goal of this work was to use a linear-quadratic model to compare single and dual-isotope implants. Ten patients were evaluated in this study. For each patient, six treatment plans were created with single or dual-isotope combinations of 1251, 103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were contoured by a physician. The biologically effective dose was used to determine the tumor control probability and normal tissue complication probabilities for each plan. Each plan was evaluated using favorable, intermediate and unfavorable radiobiological parameters. The results of the radiobiological analysis were used to compare the single and dual-isotope treatment plans. Iodine-125 only implants were seen to be most affected by changes in tumor aggressiveness. Significant differences in organ response probabilities were seen at common dose levels. It was recognized that these differences were likely a result of suboptimal initial seed strengths. After adjusting the initial seed strength to maximize complication-free tumor control the differences between isotope combinations were minimal. This result was true even for unfavorable tumors. The objective of this work was to perform a radiobiologically based comparison of single and dual-isotope prostate seed implant plans. For all isotope combinations, the plans were improved by varying the initial seed strength. For the minimally-optimized treatment plans, no substantial differences in predicted treatment outcomes were seen among the different isotope combinations.

PO-0782 TARGET DELINEATION IN RECTAL CANCER RADIOTHERAPY: RADIOBIOLOGICAL CONSEQUENCES OF ATLAS IMPLEMENTATION

Purpose/Objective: Target volume delineation variability is a major concern for cooperative groups and multi-center clinical trials. The aim of this study is to ascertain the dosimetric and radiobiologic impact of using a consensus guideline target volume delineation atlas regarding the reduction of inter-observer target delineation variation. Materials and Methods: Using a representative case and target volume delineation instructions and a standardized case derived from a proposed SWOG IMRT rectal cancer clinical trial, gross tumor volume (GTV), and clinical target volumes (CTV) were contoured by 13 physician observers. Observers were then randomly assigned to receipt (atlas) or non-receipt (control) of a cooperative-group supported consensus guideline/atlas for anorectal cancers, then instructed to re-contour the same case. PTV margin expansion and plan optimization were performed using standardized parameters from the study protocol, using sequential dynamic arc IMRT. The calculation of tumor control probability (TCP), normal tissue complication probability (NTCP), complication-free tumor control probability (P+), biologically effective uniform dose and generalized equivalent uniform dose (gEUD) was performed for all the plans. Grouped Atlas/Control TCP values were compared using Wilcoxon rank sum test and Levene’s test of variance equality for the grouped cohort GTV, CTV, and PTV inter-observer TCP grand mean (TCP’; i.e. the mean of all interobserver TCP calculations) Results: Although the variation of P+ among the members of the atlasassisted group (0.8%) was larger than that of the control group (0.5%) initially, in the second delineation the reduction of the deviation was lower for the atlas-assisted group (0.7% against 1.0%). Atlas implementation resulted in mean±SD P+ of 85.7±0.8, 78.1±2.0, and 76.8±1.1 for GTV, CTV, and PTV respectively, while for the control group the equivalent values were 85.1±0.6, 78.1±1.3, 76.4±0.6. Reduction in TCP’ variation between plans was observed with atlas use for CTV and PTV ROIs, with a reduction in TCP’ difference between plans from 13.7% (pre-atlas) to <1% (post atlas) for CTV, and from 32.5% (pre-atlas) to 7.7% (post-atlas) [p<0.01]. For the control cohort, no statistically significant differential in grand mean difference was noted, with TCP’ values for CTV of 10.2 and 6.5%, and PTV of 23.6% and 28.2% on sequential recontouring. A <1% TCP’ difference was observed in TCP for both atlas or control cohorts, suggesting minimal influence of the atlas upon GTV definition. Conclusions: The use of a visual atlas and consensus treatment guidelines in the development of rectal cancer IMRT treatment plans resulted in at least 4-fold reduction in the inter-observer dependent radiobiologic variability in TCP’ for CTV and PTV volumes. The observed differences in tumor control probability for the CTV and PTV due to the use of the atlas are potentially clinically meaningful, and suggest routine atlas implementation is a key component for reducing potential confounders of outcome in conformal radiotherapy trials. PO-0783 CONE BEAM CT BASED MARGIN GENERATION: DO WE REQUIRE DIFFERENT MARGINS FOR SUB-REGIONS OF HEAD AND NECK? A. Budrukkar 1 , R. Krishnatry 1 , K. Rajput 2 , S. Yadadu 2 , B. George 2 , S. Chaudhari 2 , S. Ghosh Laskar 1 , V. Murthy 1 , T. Gupta 1 , J. Agarwal 1

Investigating the Clinical Aspects of Using CT vs. CT-MRI Images during Organ Delineation and Treatment Planning in Prostate Cancer Radiotherapy

In order to apply highly conformal dose distributions, which are characterized by steep dose fall-offs, it is necessary to know the exact target location and extension. This study aims at evaluating the impact of using combined CT-MRI images in organ delineation compared to using CT images alone, on the clinical results. For 10 prostate cancer patients, the respective CT and MRI images at treatment position were acquired. The CTV was delineated using the CT and MRI images, separately, whereas bladder and rectum were delineated using the CT images alone. Based on the CT and MRI images, two CTVs were produced for each patient. The mutual information algorithm was used in the fusion of the two image sets. In this way, the structures drawn on the MRI images were transferred to the CT images in order to produce the treatment plans. For each set of structures of each patient, IMRT and 3D-CRT treatment plans were produced. The individual treatment plans were compared using the biologically effective uniform dose () and the complication-free tumor control probability (P(+)) concepts together with the DVHs of the targets and organs at risk and common dosimetric criteria. For the IMRT treatment, at the optimum dose level of the average CT and CT-MRI delineated CTV dose distributions, the P(+) values are 74.7% in both cases for a of 91.5 Gy and 92.1 Gy, respectively. The respective average total control probabilities, PB are 90.0% and 90.2%, whereas the corresponding average total complication probabilities, P(I) are 15.3% and 15.4%. Similarly, for the 3D-CRT treatment, the average P(+) values are 42.5% and 46.7%, respectively for a of 86.4 Gy and 86.7 Gy, respectively. The respective average P(B) values are 80.0% and 80.6%, whereas the corresponding average P(I) values are 37.4% and 33.8%, respectively. For both radiation modalities, the improvement mainly stems from the better sparing of rectum. According to these results, the expected clinical effectiveness of IMRT can be increased by a maximum ΔP(+) of around 0.9%, whereas of 3D-CRT by about 4.2% when combined CT-MRI delineation is performed instead of using CT images alone. It is apparent that in both IMRT and 3D-CRT radiation modalities, the better knowledge of the CTV extension improved the produced dose distribution. It is shown that the CTV is irradiated more effectively, while the complication probabilities of bladder and rectum, which is the principal organs at risk, are lower in the CT-MRI based treatment plans.

Response-probability volume histograms and iso-probability of response charts in treatment plan evaluation

This study aims at demonstrating a new method for treatment plan evaluation and comparison based on the radiobiological response of individual voxels. This is performed by applying them on three different cancer types and treatment plans of different conformalities. Furthermore, their usefulness is examined in conjunction with traditionally applied radiobiological and dosimetric treatment plan evaluation criteria. Three different cancer types (head and neck, breast and prostate) were selected to quantify the benefits of the proposed treatment plan evaluation method. In each case, conventional conformal radiotherapy (CRT) and intensity modulated radiotherapy (IMRT) treatment configurations were planned. Iso-probability of response charts was produced by calculating the response probability in every voxel using the linear-quadratic-Poisson model and the dose-response parameters of the corresponding structure to which this voxel belongs. The overall probabilities of target and normal tissue responses were calculated using the Poisson and the relative seriality models, respectively. The 3D dose distribution converted to a 2 Gy fractionation, D2(GY) and iso-BED distributions are also shown and compared with the proposed methodology. Response-probability volume histograms (RVH) were derived and compared with common dose volume histograms (DVH). The different dose distributions were also compared using the complication-free tumor control probability, P+, the biologically effective uniform dose, D, and common dosimetric criteria. 3D Iso-probability of response distributions is very useful for plan evaluation since their visual information focuses on the doses that are likely to have a larger clinical effect in that particular organ. The graphical display becomes independent of the prescription dose highlighting the local radiation therapy effect in each voxel without the loss of important spatial information. For example, due to the exponential nature of the Poisson distribution, cold spots in the target volumes or hot spots in the normal tissues are much easier to be identified. Response-volume histograms, as DVH, can also be derived and used for plan comparison. RVH are advantageous since by incorporating the radiobiological properties of each voxel they summarize the 3D distribution into 2D without the loss of relevant information. Thus, more clinically relevant radiobiological objectives and constraints could be defined and used in treatment planning optimization. These measures become increasingly important when dose distributions need to be designed according to the microscopic biological properties of tumor and normal tissues. The proposed methods do not aim to replace quantifiers like the probabilities of total tissue response, which ultimately are the quantities of interest to evaluate treatment success. However, iso-probability of response charts and response-probability volume histograms illustrates more clearly the difference in effectiveness between different treatment plans than the information provided by alternative dosimetric data. The use of 3D iso-probability of response distributions could serve as a good descriptor of the effectiveness of a dose distribution indicating primarily the regions in a tissue that dominate its response.

Radiobiological and Dosimetric Analysis of Daily Megavoltage CT Registration on Adaptive Radiotherapy with Helical Tomotherapy

Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (D) and the complication-free tumor control probability (P(+)). A new module of the Tomotherapy software (TomoTherapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P(+) and D concepts and plotting the tissue response probabilities vs. D a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P(+) are 48.5% and 48.9% for a D(ITV) of 53.3 Gy. The respective total control probabilities, P(B) are 56.3% and 56.5%, whereas the corresponding total complication probabilities, P(I) are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P(+) values are 53.7% and 45.7% for a D(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective P(B) values are 53.7% and 45.8%, whereas the corresponding P(I) values are ~0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P(+) values are 10.9% for a D(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective P(B) values are 14.5% and 15.3%, whereas the corresponding P(I) values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within ±2% in terms of P(+). In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.

Toolkit for Determination of Dose-response Relations, Validation of Radiobiological Parameters and Treatment Plan Optimization Based on Radiobiological Measures

Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques. One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P(+). The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head and neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head and neck cancer treatment plans. The results of the radiobiological evaluation are compared against dosimetric criteria. The presented toolkit appears to be very convenient and efficient for clinical implementation of radiobiological modeling. It can also be used for the development of a clinical data and health information database for assisting the performance of epidemiological studies and the collaboration between different institutions within research and clinical frameworks.

Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy: A Dosimetric and Radiobiological Analysis

We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V(2)0; (b) Radiobiologically by calculating the biological effective uniform dose (D) for the target and organs at risk (OAR) and the complication free tumor control probability (P(+)). As a reference for the comparative study, we included a 4D Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V(20) and MLD were respectively (13.1-/+6.9) % and (11.4-/+ 5.6)% for the MPP modality, whereas for the SPP modality they were (9.4-/+6.2) % and (7.2-/+4.7) %. On the other hand, the CGI was observed to improve by 15.3-/+13.2 and 9.6-/+10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P(+) improved on average by (6.7-/+4.9) % and (4.1-/+3.6) % for the MPP and SPP modalities, respectively while the D computed for the OAR decreased on average by (6.2-/+3.6) % and (3.8-/+3.5) % for the MPP and SPP tracking modalities, respectively. The D calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.

A graphic user interface toolkit for specification, report and comparison of dose–response relations and treatment plans using the biologically effective uniform dose

A toolkit (BEUDcal) has been developed for evaluating the effectiveness and for predicting the outcome of treatment plans by calculating the biologically effective uniform dose (BEUD) and complication-free tumor control probability. The input for the BEUDcal is the differential dose-volume histograms of organs exported from the treatment planning system. A clinical database is built for the dose–response parameters of different tumors and normal tissues. Dose–response probabilities of all the examined organs are illustrated together with the corresponding BEUDs and the P + values. Furthermore, BEUDcal is able to generate a report that simultaneously presents the radiobiological evaluation together with the physical dose indices, showing the complementary relation between the physical and radiobiological treatment plan analysis performed by BEUDcal. Comparisons between treatment plans for helical tomotherapy and multileaf collimator-based intensity modulated radiotherapy of a lung patient were demonstrated to show the versatility of BEUDcal in the assessment and report of dose–response relations.

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants.

PurposeOne of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices.Material and methodsThe quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P+ and the biologically effective uniform dose () were used for treatment plan evaluation and comparison.ResultsOur results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant (p = 0.002). The HIPO with MR treatment plans produced a higher P+ by 0.5%, which stemmed from a better sparing of the OARs by 1.0%.ConclusionsBoth the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions.

Evaluation on lung cancer patients’ adaptive planning of TomoTherapy utilising radiobiological measures and Planned Adaptive module

Adaptive radiation therapy is a promising concept that allows individualised, dynamic treatment planning based on feedback of measurements. The TomoTherapy Planned Adaptive application, integrated to the helical TomoTherapy planning system, enables calculation of actual dose delivered to the patient for each treatment fraction according to the pretreatment megavoltage computed tomography (MVCT) scan and image registration. As a result, new fractionation treatment plans are available if correction is necessary. In order to evaluate therealclinicaleffect,biologicaldoseis preferred to physical dose. A biological parameter, biologically effective uniform dose ([Formula: see text]), has the advantages of not only reporting delivered dose but also facilitating the analysis of dose-response relations, which link radiation dose to the clinical effect. Therefore, in this study, four lung patients' adaptive plans were evaluated using the [Formula: see text] in addition to physical doses estimated from the TomoTherapy Planned Adaptive module. Higher complication-free tumour control probability (P(+))(of about 8%) was observed in patients treated with larger dose-per-fraction by using the [Formula: see text] in addition to the physical dose. Moreover, a significant increase of 13.2% in the P(+) for the adaptive TomoTherapy plan in one of the lung cancer patients was also observed, which indicates the clinical benefit of adaptive TomoTherapy.

Hypofractionation: What Does It Mean for Prostate Cancer Treatment?

Using current radiobiologic models and biologic parameters, we performed an exploratory study of the clinical consequences of hypofractionation in prostate cancer radiotherapy. Four hypofractionated treatment regimens were compared with standard fractionation of 2 Gy x 39 for prostate carcinoma using a representative set of anatomical structures. The linear-quadratic model and generalized equivalent uniform dose formalism were used to calculate normalized equivalent uniform dose (gEUD(2)), from which tumor control probability and normal tissue complication probability were calculated, as well as "complication-free tumor control probability" (P+). The robustness of the results was tested for various tumor alpha/beta values and broad interval of biologic parameters such as surviving fraction after a dose of 2 Gy (SF2). A 2.5% and 5.8% decrease in NTCP for rectum and bladder, respectively, was predicted for the 6.5 Gy/fraction regimen compared with the 2 Gy/fraction. Conversely, TCP for hypofractionated regimens decreased significantly with increasing SF2 and alpha/beta. For tumor cells with SF2 = 0.4-0.5, P+ was superior for nearly all hypofractionated regimens even for alpha/beta values up to 6.5 Gy. For less responsive tumor cells (SF2 = 0.6), hypofractionation regimens were inferior to standard fractionation at much lower alpha/beta. For a sample set of anatomical structures, existing radiobiologic data and models predict improved clinical results from hypofractionation over standard fractionation not only for prostate carcinoma with low alpha/beta but also for high alpha/beta (up to 6.5 Gy) when SF2 < 0.5. Predicted results for specific patients may vary with individual anatomy, and large-scale clinical conclusions can be drawn only after performing similar analysis on an appropriate population of patients.

Comparison between Cone Beam CT Based Three-dimensional Planning and Modified Monte Carlo Dose Calculations in Intracavitary Brachytherapy for Cervical Cancer

Purpose/Objective(s): This study compares and evaluates radiation therapy plans for prostate cases using both 3D conformal treatment (3DCRT) plans and IMRT plans, to ascertain if there are dosimetric advantages to IMRT, given the current constraints. We perform a more comprehensive treatment plan evaluation using the biologically effective uniform dose together with the complication-free tumor control probability (P+). Materials/Methods: Plans were generated for ten prostate cases using the Pinnacle3, HiArt Tomotherapy, and Corvus TPSs, using two sets of IMRT constraints: from RTOG 0415, and from published data with stricter constraints. The biological equivalent of the corresponding difference in their mean doses was estimated by the Biologically Effective Uniform Dose.

A Radiobiological Perspective between IMRT and 3D Conformal Treatment of Prostate Cancer

This study compares and evaluates radiation therapy plans for prostate cases using both 3D conformal treatment (3DCRT) plans and IMRT plans, to ascertain if there are dosimetric advantages to IMRT, given the current constraints. We perform a more comprehensive treatment plan evaluation using the biologically effective uniform dose together with the complication-free tumor control probability (P+).

A radiobiological analysis of the effect of 3D versus 4D image-based planning in lung cancer radiotherapy

Dose distributions generated on a static anatomy may differ significantly from those delivered to temporally varying anatomy such as for abdominal and thoracic tumors, due largely in part to the unavoidable organ motion and deformation effects stemming from respiration. In this work, the degree of such variation for three treatment techniques, namely static conventional, gating and target tracking radiotherapy, was investigated. The actual delivered dose was approximated by planning all the phases of a 4DCT image set. Data from six (n = 6) previously treated lung cancer patients were used for this study with tumor motion ranging from 2 to 10 mm. Complete radiobiological analyses were performed to assess the clinical significance of the observed discrepancies between the 3D and 4DCT image-based dose distributions. Using the complication-free tumor control probability (P+) objective, we observed small differences in P+ between the 3D and 4DCT image-based plans (<2.0% difference on average) for the gating and static conventional regimens and higher differences in P+ (4.0% on average) for the tracking regimen. Furthermore, we observed, as a general trend, that the 3D plan underestimated the P+ values. While it is not possible to draw any general conclusions from a small patient cohort, our results suggest that there exists a patient population in which 4D planning does not provide any additional benefits beyond that afforded by 3D planning for static conventional or gated radiotherapy. This statement is consistent with previous studies based on physical dosimetric evaluations only. The higher differences observed with the tracking technique suggest that individual patient plans should be evaluated on a case-by-case basis to assess if 3D or 4D imaging is appropriate for the tracking technique.

ANALYSIS OF 4D TUMOR TRACKING RADIOTHERAPY FOR MOBILE TARGETS USING RADIOBIOLOGICAL ASSESSMENT

Purpose: To show that radiobiological analysis offers a better clinical assessment of treatment outcome compared to physical dosimetric analysis and to apply this radiobiological analysis to characterize possible benefits of tumor tracking over conventional radiotherapy. Materials: 4DCT data from six (n=6) patients with tumor motion in the range of 2-10mmwere used. Ten image sets corresponding to various phases of the respiratory cycle were derived from each 4DCT image set. A single clinician contoured the target and organs at risk on all ten phase-dependent image sets. Two plans were developed per patient based on tracking and conventional radiotherapy. In the latter, larger margins were used to account for organ motion. First, a reference image set was chosen and a plan developed based on a composite target. The plan parameters were then exported to the remaining phases and 9 other plans were created. By applying a validated deformable image registration algorithm, a deformation field was derived between each phase and the reference image which was then used to deform the dose from each of the phases to the reference phase where a weighted sum of the dose was computed to constitute the 4D dose from which a 4D DVH was developed.Tracking was characterized by reduced margins as ten different plans were developed based on target location per image set. The 4D dose and DVH were derived from all plans in a similar manner.Radiobiological assessment was based on the linear quadratic-Poisson and relative seriality models. The radiobiological parameters for each tissue were the D50, which is the dose that cause response to 50% of the patients, γ, which is the steepness of the dose-response curve, and s, which is the relative seriality. These parameters are specific for each organ and injury type and have been calculated from clinical data. The radiobiological effectiveness of each plan was quantified by the complication free tumor control probability P+ = PB PI where PB and PI are the total target response (benefit) and normal tissue complication (injury) probabilities, respectively. Four different fractionation schemes were considered; 10Gy, 6Gy, 3Gy and 2Gy per fraction for 6, 10, 20 and 30 fractions, respectively. Results: The advantages of tracking over conventional delivery were best observed using radiobiological analysis (fig 1). Higher P+ values for tracking, which decreased towards hyperfractionated schedules, were observed across all patients. For patients with tumor motion extent greater than 5mm, the relative increase in P+ were 25%±10%; 15%±7%; 8%±4%; 6%±3%, respectively for the plans with 6, 10, 20 and 30 fractions. The corresponding values for two patients with tumor motion extent less than 5mm were 10%±5%; 7%±3%; 3%±1%; 2%±2%. Conclusions: Radiobiological analysis offers a more sensitive assessment of clinical outcome and show that tracking is advantageous over conventional method with significant improvements for hypofractionated schedules. 653 poster (Physics Track)

BEUD/SECONDARY MALIGNANCY ANALYSIS: COMPARISON OF HT, MLC-BASED IMRT, AND CRT IN PROSTATE TREATMENT PLANNING

Purpose: To show that radiobiological analysis offers a better clinical assessment of treatment outcome compared to physical dosimetric analysis and to apply this radiobiological analysis to characterize possible benefits of tumor tracking over conventional radiotherapy. Materials: 4DCT data from six (n=6) patients with tumor motion in the range of 2-10mmwere used. Ten image sets corresponding to various phases of the respiratory cycle were derived from each 4DCT image set. A single clinician contoured the target and organs at risk on all ten phase-dependent image sets. Two plans were developed per patient based on tracking and conventional radiotherapy. In the latter, larger margins were used to account for organ motion. First, a reference image set was chosen and a plan developed based on a composite target. The plan parameters were then exported to the remaining phases and 9 other plans were created. By applying a validated deformable image registration algorithm, a deformation field was derived between each phase and the reference image which was then used to deform the dose from each of the phases to the reference phase where a weighted sum of the dose was computed to constitute the 4D dose from which a 4D DVH was developed.Tracking was characterized by reduced margins as ten different plans were developed based on target location per image set. The 4D dose and DVH were derived from all plans in a similar manner.Radiobiological assessment was based on the linear quadratic-Poisson and relative seriality models. The radiobiological parameters for each tissue were the D50, which is the dose that cause response to 50% of the patients, γ, which is the steepness of the dose-response curve, and s, which is the relative seriality. These parameters are specific for each organ and injury type and have been calculated from clinical data. The radiobiological effectiveness of each plan was quantified by the complication free tumor control probability P+ = PB PI where PB and PI are the total target response (benefit) and normal tissue complication (injury) probabilities, respectively. Four different fractionation schemes were considered; 10Gy, 6Gy, 3Gy and 2Gy per fraction for 6, 10, 20 and 30 fractions, respectively. Results: The advantages of tracking over conventional delivery were best observed using radiobiological analysis (fig 1). Higher P+ values for tracking, which decreased towards hyperfractionated schedules, were observed across all patients. For patients with tumor motion extent greater than 5mm, the relative increase in P+ were 25%±10%; 15%±7%; 8%±4%; 6%±3%, respectively for the plans with 6, 10, 20 and 30 fractions. The corresponding values for two patients with tumor motion extent less than 5mm were 10%±5%; 7%±3%; 3%±1%; 2%±2%. Conclusions: Radiobiological analysis offers a more sensitive assessment of clinical outcome and show that tracking is advantageous over conventional method with significant improvements for hypofractionated schedules. 653 poster (Physics Track)

Radiobiological model comparison of 3D conformal radiotherapy and IMRT plans for the treatment of prostate cancer

The main aim of radiotherapy is to deliver a dose of radiation that is high enough to destroy the tumour cells while at the same time minimising the damage to normal healthy tissues. Clinically, this has been achieved by assigning a prescription dose to the tumour volume and a set of dose constraints on critical structures. Once an optimal treatment plan has been achieved the dosimetry is assessed using the physical parameters of dose and volume. There has been an interest in using radiobiological parameters to evaluate and predict the outcome of a treatment plan in terms of both a tumour control probability (TCP) and a normal tissue complication probability (NTCP). In this study, simple radiobiological models that are available in a commercial treatment planning system were used to compare three dimensional conformal radiotherapy treatments (3D-CRT) and intensity modulated radiotherapy (IMRT) treatments of the prostate. Initially both 3D-CRT and IMRT were planned for 2 Gy/fraction to a total dose of 60 Gy to the prostate. The sensitivity of the TCP and the NTCP to both conventional dose escalation and hypo-fractionation was investigated. The biological responses were calculated using the Källman S-model. The complication free tumour control probability (P+) is generated from the combined NTCP and TCP response values. It has been suggested that the alpha/beta ratio for prostate carcinoma cells may be lower than for most other tumour cell types. The effect of this on the modelled biological response for the different fractionation schedules was also investigated.

Assessing Four-dimensional Radiotherapy Planning and Respiratory Motion-induced Dose Difference Based on Biologically Effective Uniform Dose

Four-dimensional (4D) radiotherapy is considered as a feasible and ideal solution to accommodate intra-fractional respiratory motion during conformal radiation therapy. With explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy, 4D treatment planning in principle provides better dose conformity. However, the clinical benefits of developing 4D treatment plans in terms of tumor control rate and normal tissue complication probability as compared to other treatment plans based on CT images of a fixed respiratory phase remains mostly unproven. The aim of our study is to comprehensively evaluate 4D treatment planning for nine lung tumor cases with both physical and biological measures using biologically effective uniform dose (D =) together with complication-free tumor control probability, P+. Based on the examined lung cancer patients and PTV margin applied, we found similar but not identical curves of DVH, and slightly different mean doses in tumor (up to 1.5%) and normal tissue in all cases when comparing 4D, P0%, and P50% plans. When it comes to biological evaluations, we did not observe definitively PTV size dependence in P+ among these nine lung cancer patients with various sizes of PTV. Moreover, it is not necessary that 4D plans would have better target coverage or higher P+ as compared to a fixed phase IMRT plan. However, on the contrary to significant deviations in P+ (up to 14.7%) observed if delivering the IMRT plan made at end-inhalation incorrectly at end-exhalation phase, we estimated the overall P+, PB, and PI for 4D composite plans that have accounted for intra-fractional respiratory motion.

Calculation of the Transit Dose in HDR Brachytherapy Based on Monte Carlo Simulations

The Monte Carlo method, which is the gold standard for accurate dose calculations in radiotherapy, was used to obtain the transit doses around a high dose rate (HDR) brachytherapy implant with thirteen dwell points. The midpoints of each of the inter-dwell separations, of step size 0.25 cm, were representative of the positions of the dynamic brachytherapy source, so the average dose rates were calculated when the geometrical centre of the moving source was at each of these points. The dose rates were then transformed into transit doses and our output compared to outputs from other methods. There were especially high discrepancies between our results and the Sievert Integral results, ranging from –32 to –21% for the examples considered. The discrepancies could be much higher for implants of longer lengths where contributions from points near the longitudinal axis of the source become more important. These translate into errors of more than 4 % in the prescribed dose and could have significant impact on complication free tumour control. The Monte Carlo method is therefore recommended for the evaluation of transit doses around brachytherapy implants. Other methods which do not exhibit the same level of accuracy as the Monte Carlo method must be used with great caution. Journal of the Ghana Science Association Vol. 10 (2) 2008: pp. 134-138