Differences In Tumor Control Probability Research Articles

Tumor control probability and the utility of 4D vs 3D dose calculations for stereotactic body radiotherapy for lung cancer

Four-dimensional (4D) dose calculations for lung cancer radiotherapy have been technically feasible for a number of years but have not become standard clinical practice. The purpose of this study was to determine if clinically significant differences in tumor control probability (TCP) exist between 3D and 4D dose calculations so as to inform the decision whether 4D dose calculations should be used routinely for treatment planning. Radiotherapy plans for Stage I-II lung cancer were created for 8 patients. Clinically acceptable treatment plans were created with dose calculated on the end-exhale 4D computed tomography (CT) phase using a Monte Carlo algorithm. Dose was then projected onto the remaining 9 phases of 4D-CT using the Monte Carlo algorithm and accumulated onto the end-exhale phase using commercially available deformable registration software. The resulting dose-volume histograms (DVH) of the gross tumor volume (GTV), planning tumor volume (PTV), and PTVsetup were compared according to target coverage and dose. The PTVsetup was defined as a volume including the GTV and a margin for setup uncertainties but not for respiratory motion. TCPs resulting from these DVHs were estimated using a wide range of alphas, betas, and tumor cell densities. Differences of up to 5Gy were observed between 3D and 4D calculations for a PTV with highly irregular shape. When the TCP was calculated using the resulting DVHs for fractionation schedules typically used in stereotactic body radiation therapy (SBRT), the TCP differed at most by 5% between 4D and 3D cases, and in most cases, it was by less than 1%. We conclude that 4D dose calculations are not necessary for most cases treated with SBRT, but they might be valuable for irregularly shaped target volumes. If 4D calculations are used, 4D DVHs should be evaluated on volumes that include margin for setup uncertainty but not respiratory motion.

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

Is it beneficial to selectively boost high-risk tumor subvolumes? A comparison of selectively boosting high-risk tumor subvolumes versus homogeneous dose escalation of the entire tumor based on equivalent EUD plans

Purpose. To quantify and compare expected local tumor control and expected normal tissue toxicities between selective boosting IMRT and homogeneous dose escalation IMRT for the case of prostate cancer. Methods. Four different selective boosting scenarios and three different high-risk tumor subvolume geometries were designed to compare selective boosting and homogeneous dose escalation IMRT plans delivering the same equivalent uniform dose (EUD) to the entire PTV. For each scenario, differences in tumor control probability between both boosting strategies were calculated for the high-risk tumor subvolume and remaining low-risk PTV, and were visualized using voxel based iso-TCP maps. Differences in expected rectal and bladder complications were quantified using radiobiological indices (generalized EUD (gEUD) and normal tissue complication probability (NTCP)) as well as %-volumes. Results. For all investigated scenarios and high-risk tumor subvolume geometries, selective boosting IMRT improves expected TCP compared to homogeneous dose escalation IMRT, especially when lack of control of the high-risk tumor subvolume could be the cause for tumor recurrence. Employing, selective boosting IMRT significant increases in expected TCP can be achieved for the high-risk tumor subvolumes. The three conventional selective boosting IMRT strategies, employing physical dose objectives, did not show significant improvement in rectal and bladder sparing as compared to their counterpart homogeneous dose escalation plans. However, risk-adaptive optimization, utilizing radiobiological objective functions, resulted in reduction in NTCP for the rectum when compared to its corresponding homogeneous dose escalation plan. Conclusions. Selective boosting is a more effective method than homogeneous dose escalation for achieving optimal treatment outcomes. Furthermore, risk-adaptive optimization increases the therapeutic ratio as compared to conventional selective boosting IMRT.

IMRT boost dose planning on dominant intraprostatic lesions: Gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI

To demonstrate the theoretical feasibility of integrating two functional prostate magnetic resonance imaging (MRI) techniques (dynamic contrast-enhanced MRI [DCE-MRI] and 1H-spectroscopic MRI [MRSI]) into inverse treatment planning for definition and potential irradiation of a dominant intraprostatic lesion (DIL) as a biologic target volume for high-dose intraprostatic boosting with intensity-modulated radiotherapy (IMRT). In 5 patients, four gold markers were implanted. An endorectal balloon was inserted for both CT and MRI. A DIL volume was defined by DCE-MRI and MRSI using different prostate cancer-specific physiologic (DCE-MRI) and metabolic (MRSI) parameters. CT-MRI registration was performed automatically by matching three-dimensional gold marker surface models with the iterative closest point method. DIL-IMRT plans, consisting of whole prostate irradiation to 70 Gy and a DIL boost to 90 Gy, and standard IMRT plans, in which the whole prostate was irradiated to 78 Gy were generated. The tumor control probability and rectal wall normal tissue complication probability were calculated and compared between the two IMRT approaches. Combined DCE-MRI and MRSI yielded a clearly defined single DIL volume (range, 1.1-6.5 cm3) in all patients. In this small, selected patient population, no differences in tumor control probability were found. A decrease in the rectal wall normal tissue complication probability was observed in favor of the DIL-IMRT plan versus the plan with IMRT to 78 Gy. Combined DCE-MRI and MRSI functional image-guided high-dose intraprostatic DIL-IMRT planned as a boost to 90 Gy is theoretically feasible. The preliminary results have indicated that DIL-IMRT may improve the therapeutic ratio by decreasing the normal tissue complication probability with an unchanged tumor control probability. A larger patient population, with more variations in the number, size, and localization of the DIL, and a feasible mechanism for treatment implementation has to be studied to extend these preliminary tumor control and toxicity estimates.

IMRT versus conventional 3DCRT on prostate and normal tissue dosimetry using an endorectal balloon for prostate immobilization

This study was undertaken to compare prostate and normal tissue dosimetry in prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and conventional 3-dimensional conformal radiotherapy (3DCRT) using an endorectal balloon for prostate immobilization. Ten prostate cancer patients were studied using both IMRT and conventional 3DCRT at Houston Veterans Affairs Medical Center. For IMRT, the prescription was 70 Gy at 2 Gy/fraction at the 83.4% isodose line, allowing no more than 15% of the rectum and 33% of the bladder to receive above 68 and 65 Gy, respectively. For conventional 3DCRT, a 6-field arrangement with lateral and oblique fields was used to deliver 76 Gy at 2Gy/fraction, ensuring complete tumor coverage by the 72-Gy isodose line. Mean doses for prostate and seminal vesicles were 75.10 and 75.11 Gy, respectively, for IMRT and 75.40 and 75.02 Gy, respectively, for 3DCRT ( p > 0.218). 3DCRT delivered significantly higher doses to 33%, 50%, and 66% volumes of rectum by 3.55, 6.64, and 10.18 Gy, respectively ( p < 0.002), and upper rectum by 7.26, 9.86, and 9.16 Gy, respectively ( p < 0.007). 3DCRT also delivered higher doses to femur volumes of 33% and 50% by 9.38 and 10.19 Gy, respectively, ( p < 0.001). Insignificant differences in tumor control probability (TCP) values between IMRT and 3DCRT were calculated for prostate ( p = 0.320) and seminal vesicles ( p = 0.289). Compared to 3DCRT, IMRT resulted in significantly reduced normal tissue complication probability (NTCP) only for upper rectum ( p = 0.025) and femurs ( p = 0.021). This study demonstrates that IMRT achieves superior normal tissue avoidance, especially for rectum and femurs compared to 3DCRT, with comparable target dose escalation.

Investigation of the added value of high-energy electrons in intensity-modulated radiotherapy: four clinical cases

Purpose : Intensity-modulated radiotherapy (IMRT) with photon beams is currently pursued in many clinics. Theoretically, inclusion of intensity- and energy-modulated high-energy electron beams (15–50 MeV) offers additional possibilities to improve radiotherapy treatments of deep-seated tumors. In this study the added value of high-energy electron beams in IMRT treatments was investigated. Methods and Materials : In a comparative treatment planning study, conventional treatment plans and various types of IMRT plans were constructed for four clinical cases (cancer of the bladder, pancreas, chordoma of the sacrum, and breast). The conventional plans were used for the actual treatment of the patients. The IMRT plans were optimized using the Orbit optimization code (Löf et al ., 2000) with a radiobiologic objective function. The IMRT plans were either photon or combined electron and photon beam plans, with or without dose homogeneity constraints assuming standard or increased radiosensitivities of organs at risk. Results : Large improvements in expected treatment outcome are found using IMRT plans compared to conventional plans, but differences in tumor control probability (TCP) and normal tissue complication probabilities (NTCP) values between IMRT plans with and without electrons are small. However, the use of electrons improves the dose-volume histograms for organs at risk, especially at lower dose levels (e.g., 0–40 Gy). Conclusions : This preliminary study indicates that addition of higher energy electrons to IMRT can only marginally improve treatment outcome for the selected cases. The dose-volume histograms of organs at risk show improvements for IMRT with higher energy electrons, which may reduce tumor induction but does not substantially reduce NTCP.