Impact of dose calculation models on radiotherapy outcomes and quality adjusted life years for lung cancer treatment: do we need to measure radiotherapy outcomes to tune the radiobiological parameters of a normal tissue complication probability model? (original) (raw)

The influence of beam model differences in the comparison of dose calculation algorithms for lung cancer treatment planning

Physics in Medicine and Biology, 2005

In this study, we show that beam model differences play an important role in the comparison of dose calculated with various algorithms for lung cancer treatment planning. These differences may impact the accurate correlation of dose with clinical outcome. To accomplish this, we modified the beam model penumbral parameters in an equivalent path length (EPL) algorithm and subsequently compared the EPL doses with those generated with Monte Carlo (MC). A single AP beam was used for beam fitting. Two different beam models were generated for EPL calculations: (1) initial beam model (init fit) and (2) optimized beam model (best fit), with parameters optimized to produce the best agreement with MC calculated profiles at several depths in a water phantom. For the 6 MV, AP beam, EPL(init fit) calculations were on average within 2%/2 mm (1.4 mm max.) agreement with MC; the agreement for EPL(best fit) was 2%/0.5 mm (1.0 mm max.). For the 15 MV, AP beam, average agreements with MC were 5%/2 mm (7.4%/2.6 mm max.) for EPL(init fit) and 2%/1.0 mm (1.3 mm max.) for EPL(best fit). Treatment planning was performed using a realistic lung phantom using 6 and 15 MV photons. In all homogeneous phantom plans, EPL(best fit) calculations were in better agreement with MC. In the heterogeneous 6 MV plan, differences between EPL(best fit and init fit) and MC were significant for the tumour. The EPL(init fit), unlike the EPL(best fit) calculation, showed large differences in the lung relative to MC. For the 15 MV heterogeneous plan, clinically important differences were found between EPL(best fit or init fit) and MC for tumour and lung, suggesting that the algorithmic difference in inhomogeneous tissues was most influential in this case. Finally, an example is presented for a 6 MV conformal clinical treatment plan. In both homogeneous and heterogeneous cases, differences between EPL(best fit) and MC for lung tissues were smaller compared to those between EPL(init fit) and MC. Although the extent to 0031-9155/05/050801+15$30.00

Effect of Normal Lung Definition on Lung Dosimetry and Lung Toxicity Prediction in Radiation Therapy Treatment Planning

International Journal of Radiation Oncology*Biology*Physics, 2013

Purpose-This study aimed to compare lung dose-volume histogram (DVH) parameters such as mean lung dose (MLD) and the lung volume receiving ≥20 Gy (V20) of commonly used definitions of normal lung in terms of tumor/target subtraction and to determine to what extent they differ in predicting radiation pneumonitis (RP). Methods and Materials-One hundred lung cancer patients treated with definitive radiation therapy were assessed. The gross tumor volume (GTV) and clinical planning target volume (PTV c) were defined by the treating physician and dosimetrist. For this study, the clinical target volume (CTV) was defined as GTV with 8-mm uniform expansion, and the PTV was defined as CTV with an 8-mm uniform expansion. Lung DVHs were generated with exclusion of targets: (1) GTV (DVH G); (2) CTV (DVH C); (3) PTV (DVH P); and (4) PTV c (DVH Pc). The lung DVHs, V20s, and MLDs from each of the 4 methods were compared, as was their significance in predicting radiation pneumonitis of grade 2 or greater (RP2). Results-There are significant differences in dosimetric parameters among the various definition methods (all Ps<.05). The mean and maximum differences in V20 are 4.4% and 12.6% (95% confidence interval 3.6%-5.1%), respectively. The mean and maximum differences in MLD are 3.3 Gy and 7.5 Gy (95% confidence interval, 1.7-4.8 Gy), respectively. MLDs of all methods are highly correlated with each other and significantly correlated with clinical RP2, although V20s are not. For RP2 prediction, on the receiver operating characteristic curve, MLD from DVH G (MLD G has a greater area under curve of than MLD from DVH C (MLD C) or DVH P (MLD P). Limiting RP2 to 30%, the threshold is 22.4, 20.6, and 18.8 Gy, for MLD G , MLD C , and MLD P , respectively.

The significance of the choice of Radiobiological (NTCP) models in treatment plan objective functions

Australasian Physics & Engineering Sciences in Medicine, 2009

A Clinician's discrimination between radiation therapy treatment plans is traditionally a subjective process, based on experience and existing protocols. A more objective and quantitative approach to distinguish between treatment plans is to use radiobiological or dosimetric objective functions, based on radiobiological or dosimetric models. The efficacy of models is not well understood, nor is the correlation of the rank of plans resulting from the use of models compared to the traditional subjective approach. One such radiobiological model is the Normal Tissue Complication Probability (NTCP). Dosimetric models or indicators are more accepted in clinical practice. In this study, three radiobiological models, Lyman NTCP, critical volume NTCP and relative seriality NTCP, and three dosimetric models, Mean Lung Dose (MLD) and the Lung volumes irradiated at 10Gy (V 10 ) and 20Gy (V 20 ), were used to rank a series of treatment plans using, harm to normal (Lung) tissue as the objective criterion. None of the models considered in this study showed consistent correlation with the Radiation Oncologists plan ranking. If radiobiological or dosimetric models are to be used in objective functions for lung treatments, based on this study it is recommended that the Lyman NTCP model be used because it will provide most consistency with traditional clinician ranking.

The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: Implications for tumour coverage

Radiotherapy and Oncology, 2009

Purpose: To evaluate against Monte-Carlo the performance of various dose calculations algorithms regarding lung tumour coverage in stereotactic body radiotherapy (SBRT) conditions. Materials and methods: Dose distributions in virtual lung phantoms have been calculated using four commercial Treatment Planning System (TPS) algorithms and one Monte Carlo (MC) system (EGSnrc). We compared the performance of the algorithms in calculating the target dose for different degrees of lung inflation. The phantoms had a cubic 'body' and 'lung' and a central 2-cm diameter spherical 'tumour' (the body and tumour have unit density). The lung tissue was assigned five densities (q lung ): 0.01, 0.1, 0.2, 0.4 and 1 g=cm 3 . Four-field treatment plans were calculated with 6-and 18 MV narrow beams for each value of q lung . We considered the Pencil Beam Convolution (PBC Ecl ) and the Analytical Anisotropic Algorithm (AAA Ecl ) from Varian Eclipse and the Pencil Beam Convolution (PBC OMP ) and the Collapsed Cone Convolution (CCC OMP ) algorithms from Oncentra MasterPlan.

Radiation Dose Prescription for Non–Small-Cell Lung Cancer According to Normal Tissue Dose Constraints: An In Silico Clinical Trial

International Journal of Radiation Oncology*Biology*Physics, 2008

Purpose: Local tumor recurrence remains a major problem in patients with inoperable non-small-cell lung cancer undergoing radiotherapy. We investigated the theoretical gain in the estimated tumor control probability (TCP) using an individualized maximal tolerable dose (MTD) prescription, for both conventional and accelerated fractionation schemes. Methods and Materials: For 64 non-small-cell lung cancer patients, five treatment plans were compared, dependent on the normal tissue dose constraints for the lung and spinal cord. The first two used a classic fractionation (2 Gy/d, 5 d/wk) to a total dose of 60 Gy (QD classic ) or determined by the individualized MTD (QD MTD ). The third scheme assumed a hypofractionated schedule of 2.75-Gy fractions (QD hypofr ). The fourth and fifth assumed hyperfractionation and acceleration (1.8 Gy twice daily, either BID classic or BID MTD ). The TCPs for the groups of patients were estimated. Results: The mean biologic equivalent dose in 2-Gy fractions for tumor, corrected for accelerated repopulation was significantly greater for the BID MTD scheme (62.1 Gy) than for any other scheme (QD classic , 47.5 Gy; QD MTD , 52.0 Gy; QD hypofr , 56.9 Gy; and BID classic , 56.9 Gy; p < 0.001). Although both dose-escalation (QD MTD ) and hypofractionation (QD hypofr ) resulted in an increase in the mean estimated TCP of 5.6% (p < 0.001) and 14.6% (p < 0.001), respectively, compared with QD classic , the combination of escalation and acceleration (BID MTD ) improved the mean estimated TCP by 26.4% (p < 0.001). Conclusion: The results of this planning study showed a large gain in the estimated TCP using an MTD scheme with 1.8-Gy fractions BID compared with other fractionation schedules. Clinical studies implementing this concept are ongoing. Ó 2008 Elsevier Inc.

Tissue Heterogeneity in IMRT Dose Calculation for Lung Cancer

Medical Dosimetry, 2011

The aim of this study was to evaluate the differences in accuracy of dose calculation between 3 commonly used algorithms, the Pencil Beam algorithm (PB), the Anisotropic Analytical Algorithm (AAA), and the Collapsed Cone Convolution Superposition (CCCS) for intensity-modulated radiation therapy (IMRT). The 2D dose distributions obtained with the 3 algorithms were compared on each CT slice pixel by pixel, using the MATLAB code (The MathWorks, Natick, MA) and the agreement was assessed with the ␥ function. The effect of the differences on dose-volume histograms (DVHs), tumor control, and normal tissue complication probability (TCP and NTCP) were also evaluated, and its significance was quantified by using a nonparametric test. In general PB generates regions of over-dosage both in the lung and in the tumor area. These differences are not always in DVH of the lung, although the Wilcoxon test indicated significant differences in 2 of 4 patients. Disagreement in the lung region was also found when the ⌫ analysis was performed. The effect on TCP is less important than for NTCP because of the slope of the curve at the level of the dose of interest. The effect of dose calculation inaccuracy is patient-dependent and strongly related to beam geometry and to the localization of the tumor. When multiple intensity-modulated beams are used, the effect of the presence of the heterogeneity on dose distribution may not always be easily predictable.

The relationship between dosimetric factors, side effects, and survival in patients with non–small cell lung cancer treated with definitive radiotherapy

Medical Dosimetry, 2017

The patients with non-small cell lung cancer (NSCLC) treated with definitive conformal radiotherapy (RT) were evaluated in terms of side effects and survival. Normal tissue complication probability (NTCP) was calculated for 68 patients treated between 2009 and 2012. Clinical and dosimetric factors were analyzed. The median dose of 63 Gy (range: 54 to 70 Gy) was given with conformal RT with blocks (n = 37), 3-dimensional conformal RT (3DCRT) (n = 11), or intensity-modulated RT (IMRT) (n = 20). Acute grade 1 to 2 radiation pneumonitis (RP) was seen in 13% of the patients. No significant relationship was found between RP and treatment and dosimetric factors (p > 0.05). There was a positive correlation between median "mean lung dose" (MLD) (17 Gy), lung V30 (20.5%), and NTCP (14%) (p < 0.001). Median and 2-year overall survival (OS) and progression-free survival (PFS) were 27 and 18 months and 51% and 42%, respectively. In univariate analysis, significant dose range for survival was found between 59.4 and 63 Gy (p < 0.01). In multivariate analysis, response (p = 0.001), fraction dose of 1.8 Gy (p = 0.002), MLD <18 Gy (p = 0.04) for OS and response (p < 0.001), total dose > 59.4 Gy (p = 0.01), and tumor biologically effective dose (BED)3(Gy) ≤ 100.8 (p = 0.01) for PFS were found to be favorable factors. In our study, we found a linear correlation between NTCP and MLD for RP risk estimation in patients with NSCLC. Therapeutic dose range where MLD can be kept under 20 Gy with significant survival benefit was found between 59.4 and 63 Gy. Increased therapeutic efficacy will be possible using risk-adaptive RT techniques.

Dosimetric Verification of Stereotactic Body Radiotherapy Treatment Plans For Early Stage Non-Small Cell Lung Cancer Using Monte Carlo Simulation

Calculation of the absorbed dose delivered to a patient during radiotherapy treatment is extremely important and has a direct impact on the treatment outcome. The calculation of the dose to tumour and normal tissues is particularly challenging for lung cancer treatments where large density variations can exist. Previous studies have compared different algorithms used for dose calculation in the treatment planning system (TPS). However, the impact of dose calculation accuracy on treatment outcomes prediction has not been widely studied, especially in regards to lung stereotactic body radiotherapy treatment (SBRT). This research aims to investigate the accuracy of the collapsed cone convolution algorithm employed in the Pinnacle 3 TPS for dose calculation of lung SBRT plans and the potential impact of any dose uncertainties on treatment outcomes prediction. For this purpose, a EGSnrc/BEAMnrc Monte Carlo model of an Elekta Axesse linear accelerator equipped with the Beam Modulator collimation system was developed and commissioned. The commissioned model was used to perform Monte Carlo simulations of the dose distribution of twenty early stage non-small cell lung cancer patient plans. The dosimetric parameters of the planning treatment volume (PTV) and organs at risk (OARs) were evaluated and compared with the TPS calculation. The effects of dose calculation uncertainties to the tumour control probability (TCP) and normal tissue complication probability (NTCP) were modelled using the Linear Quadratic Poisson TCP model and the Lyman-Kutcher-Burman NTCP model. The study found that no significant difference was observed in the PTV dose parameters between the TPS and Monte Carlo calculations. An agreement of ±6% was observed for the PTV coverage of the prescribed isodose, and even greater agreement of ±2% for the coverage of the 90% prescribed isodose. The TPS algorithm tended to overestimate the dose to OARs, with the exception of normal lung tissue, brachial plexus, and pericardium. A significant difference was mostly observed for the maximum point dose parameter. However, most dose parameters to OARs were still below the dose constraints outlined in the RTOG 1021 protocol for both the TPS and Monte Carlo plans. The only significant dose constraint violation was observed for the maximum point dose to the ribs, occurring in plans with a tumour located closest to the chest wall. The radiobiological analysis showed that the TCP parameters were more sensitive to dose calculation uncertainties than NTCP