Purpose
Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer ...patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery.
Methods
A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built.
Results
The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65–0.85), 0.68 (95%CI: 0.57–0.80), and 0.68 (95%CI: 0.58–0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51–0.69), 0.64 (95%CI: 0.53–0.75), and 0.65 (95%CI: 0.50–0.72) for the CT, the PET, and the PET+CT images, respectively.
Conclusions
A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery.
Purpose
To evaluate the ability of CT and PET radiomics features to classify lung lesions as primary or metastatic, and secondly to differentiate histological subtypes of primary lung cancers.
...Methods
A cohort of 534 patients with lung lesions were retrospectively studied. Radiomics texture features were extracted using the LIFEx package from semiautomatically segmented PET and CT images. Histology data were recorded in all patients. The patient cohort was divided into a training and a validation group and linear discriminant analysis (LDA) was performed to classify the lesions using both direct and backward stepwise methods. The robustness of the procedure was tested by repeating the entire process 100 times with different assignments to the training and validation groups. Scoring metrics included analysis of the receiver operating characteristic curves in terms of area under the curve (AUC), sensitivity, specificity and accuracy.
Results
Radiomics features extracted from CT and PET datasets were able to differentiate primary tumours from metastases in both the training and the validation group (AUCs 0.79 ± 0.03 and 0.70 ± 0.04, respectively, from the CT dataset; AUCs 0.92 ± 0.01 and 0.91 ± 0.03, respectively, from the PET dataset). The AUC cut-off thresholds identified by LDA using direct and backward elimination strategies were −0.79 ± 0.06 and −0.81 ± 0.08, respectively (CT dataset) and −0.69 ± 0.05 and −0.68 ± 0.04, respectively (PET dataset). For differentiation between primary subgroups based on CT features, the AUCs in the training and validation groups were 0.81 ± 0.02 and 0.69 ± 0.04 for adenocarcinoma (Adc) vs. squamous cell carcinoma (Sqc) or “Other”, 0.85 ± 0.02 and 0.70 ± 0.05 for Sqc vs. Adc or Other, and 0.77 ± 0.03 and 0.57 ± 0.05 for Other vs. Adc or Sqc. The same analyses for the PET data revealed AUCs of 0.90 ± 0.10 and 0.80 ± 0.04, 0.80 ± 0.02 and 0.61 ± 0.06, and 0.97 ± 0.01 and 0.88 ± 0.04, respectively.
Conclusion
PET radiomics features were able to differentiate between primary and metastatic lung lesions and showed the potential to identify primary lung cancer subtypes.
Highlights • The literature regarding the lung SBRT dose calculation algorithm accuracy is reviewed. • The small field and low density problems are analysed. • A summarizing example focuses on the ...main differences and aspects of the main three classes of dose calculation algorithms.
To assess the clinical impact of the Acuros XB algorithm (implemented in the Varian Eclipse treatment-planning system) in non-small-cell lung cancer (NSCLC) cases.
A CT dataset of 10 patients ...presenting with advanced NSCLC was selected and contoured for planning target volume, lungs, heart, and spinal cord. Plans were created for 6-MV and 15-MV beams using three-dimensional conformal therapy, intensity-modulated therapy, and volumetric modulated arc therapy with RapidArc. Calculations were performed with Acuros XB and the Anisotropic Analytical Algorithm. To distinguish between differences coming from the different heterogeneity management and those coming from the algorithm and its implementation, all the plans were recalculated assigning Hounsfield Unit (HU) = 0 (Water) to the CT dataset.
Differences in dose distributions between the two algorithms calculated in Water were <0.5%. This suggests that the differences in the real CT dataset can be ascribed mainly to the different heterogeneity management, which is proven to be more accurate in the Acuros XB calculations. The planning target dose difference was stratified between the target in soft tissue, where the mean dose was found to be lower for Acuros XB, with a range of 0.4% ± 0.6% (intensity-modulated therapy, 6 MV) to 1.7% ± 0.2% (three-dimensional conformal therapy, 6 MV), and the target in lung tissue, where the mean dose was higher for 6 MV (from 0.2% ± 0.2% to 1.2% ± 0.5%) and lower for 15 MV (from 0.5% ± 0.5% to 2.0% ± 0.9%). Mean doses to organs at risk presented differences up to 3% of the mean structure dose in the worst case. No particular or systematic differences were found related to the various modalities. Calculation time ratios between calculation time for Acuros XB and the Anisotropic Analytical Algorithm were 7 for three-dimensional conformal therapy, 5 for intensity-modulated therapy, and 0.2 for volumetric modulated arc therapy with RapidArc.
The availability of Acuros XB could improve patient dose estimation, increasing the data consistency of clinical trials.
To evaluate the feasibility of high-dose stereotactic body radiation therapy (SBRT) in the treatment of unresectable liver metastases.
Patients with 1 to 3 liver metastases, with maximum individual ...tumor diameters less than 6 cm and a Karnofsky Performance Status of at least 70, were enrolled and treated by SBRT on a phase 2 clinical trial. Dose prescription was 75 Gy on 3 consecutive days. SBRT was delivered using the volumetric modulated arc therapy by RapidArc (Varian, Palo Alto, CA) technique. The primary end-point was in-field local control. Secondary end-points were toxicity and survival.
Between February 2010 and September 2011, a total of 61 patients with 76 lesions were treated. Among the patients, 21 (34.3%) had stable extrahepatic disease at study entry. The most frequent primary sites were colorectal (45.9%) and breast (18%). Of the patients, 78.7% had 1 lesion, 18.0% had 2 lesions, and 3.3% had 3 lesions. After a median of 12 months (range, 2-26 months), the in-field local response rate was 94%. The median overall survival rate was 19 months, and actuarial survival at 12 months was 83.5%. None of the patients experienced grade 3 or higher acute toxicity. No radiation-induced liver disease was detected. One patient experienced G3 late toxicity at 6 months, resulting from chest wall pain.
SBRT for unresectable liver metastases can be considered an effective, safe, and noninvasive therapeutic option, with excellent rates of local control and a low treatment-related toxicity.
A study was realised to evaluate and determine relative figures of merit of a new algorithm for photon dose calculation when applied to inhomogeneous media.
The new Acuros XB algorithm implemented in ...the Varian Eclipse treatment planning system was compared against a Monte Carlo method (VMC++), and the Analytical Anisotropic Algorithm (AAA). The study was carried out in virtual phantoms characterized by simple geometrical structures. An insert of different material and density was included in a phantom built of skeletal-muscle and HU = 0 (setting "A"): Normal Lung (lung, 0.198 g/cm3); Light Lung (lung, 0.035 g/cm3); Bone (bone, 1.798 g/cm3); another phantom (setting "B") was built of adipose material and including thin layers of bone (1.85 g/cm3), adipose (0.92 g/cm3), cartilage (1.4745 g/cm3), air (0.0012 g/cm3). Investigations were performed for 6 and 15 MV photon beams, and for a large (13 × 13 cm2) and a small (2.8 × 13 cm2) field.
Results are provided in terms of depth dose curves, transverse profiles and Gamma analysis (3 mm/3% and 2 mm/2% distance to agreement/dose difference criteria) in planes parallel to the beam central axis; Monte Carlo simulations were assumed as reference. Acuros XB gave an average gamma agreement, with a 3 mm/3% criteria, of 100%, 86% and 100% for Normal Lung, Light Lung and Bone settings, respectively, and dose to medium calculations. The same figures were 86%, 11% and 100% for AAA, where only dose rescaled to water calculations are possible.
In conclusion, Acuros XB algorithm provides a valid and accurate alternative to Monte Carlo calculations for heterogeneity management.
To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma.
A cohort of 100 patients was included in this ...retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index.
A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively.
A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.
Purpose:
Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and ...to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis.
Methods:
Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2; MLC-defined: 0.5 × 0.5 cm2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2. MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed.
Results:
Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the best agreement averaged over all the energies, of −3.9% and 0.2% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms.
Conclusions:
For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC-defined fields as small as 0.5 × 0.5 cm2. Similar agreement was found for AAA for fields as small as 1 × 1 cm2.
Objectives
To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC) unsuitable for standard loco-regional therapies.
...Materials and methods
Patients with 1–3 inoperable HCC lesions with diameter ≤6 cm were treated by SBRT. According to lesions size and liver function, two prescription regimens were adopted: 48–75 Gy in three fractions or 36–60 Gy in six fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points of this study were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and progression-free survival (PFS).
Results
Forty-three patients with 63 HCC lesions were irradiated. All patients had Child–Turcotte–Pugh class A or B disease. Thirty lesions (48 %) were treated with 48–75 Gy in three consecutive fractions, and 33 (52 %) received 36–60 Gy in six fractions. Median follow-up was 8 months (range 3–43 months). Actuarial LC at 6, 12 and 24 months was 94.2 ± 3.3, 85.8 ± 5.5 and 64.4 ± 11.5 %, respectively. A biological equivalent dose (BED) >100 Gy and GTV size were significant prognostic factors for LC in univariate analysis (
p
< 0.001 and
p
< 0.02). Median OS was 18.0 ± 5.8 months. Actuarial OS at 6, 12 and 24 months was 91.1 ± 4.9, 77.9 ± 8.2 and 45.3 ± 14.0 %, respectively. Univariate analysis showed that OS is correlated with LC (
p
< 0.04), BED >100 (
p
< 0.05) and cumulative gross tumor volume GTV <5 cm (
p
< 0.04). Median PFS was 8 months, with a 1-year PFS rate of 41 %. A significant (≥grade 3) toxicity was observed in seven patients (16 %) 2–6 months after the completion of the treatment. No classic radiation-induced liver disease was observed.
Conclusion
Stereotactic body radiation therapy is a safe and effective therapeutic option for HCC lesions unsuitable to standard loco-regional therapies, with acceptable local control rates and low treatment-related toxicity. The significant correlation between LC and higher doses and between LC and OS supports the clinical value of SBRT in these patients.
Purpose: In breast radiotherapy with intensity modulation, it is a well established practice to extend the dose fluence outside the limit of the body contour to account for small changes in size and ...position of the target and the rest of the tissues due to respiration or to possible oedema. A simple approach is not applicable with RapidArc volumetric modulated arc therapy not being based on a fixed field fluence delivery. In this study, a viable technical strategy to account for this need is presented.Methods: RapidArc (RA) plans for six breast cancer patients (three right and three left cases), were optimized (PRO version III) on the original CT data set (O) and on an alternative CT (E) generated with an artificial expansion (and assignment of soft-tissue equivalent HU) of 10 mm of the body in the breast region and of the PTV contours toward the external direction. Final dose calculations for the two set of plans were performed on the same original CT data set O, normalizing the dose prescription (50 Gy) to the target mean. In this way, two treatment plans on the same CT set O for each patient were obtained: the no action plan (OO) and the alternative plan based on an expanded optimization (EO). Fixing MU, these two plans were then recomputed on the expanded CT data set and on an intermediate one (with expansion = 5 mm), to mimic, possible changes in size due to edema during treatment or residual displacements due to breathing not properly controlled. Aim of the study was to quantify the robustness of this planning strategy on dose distributions when either the OO or the EO strategies were adopted. For all the combinations, a DVH analysis of all involved structures is reported.Results: I. The two optimization approaches gave comparable dose distributions on the original CT data set. II. When plans were evaluated on the expanded CTs (mimicking the presence of edema), the EO approach showed improved target coverage if compared to OO: on CT_10 mm, D
V = 98% % = 92.5 ± 0.9 and 68.5 ± 3.1, respectively, for EO and OO. Minor changes were registered in organs at risk sparing for both EO and OO. III. From dose distributions and DVHs, EO approach allowed to irradiate at near to prescription levels also the expanded fraction of the target: this would account also for residual intrafraction movements.Conclusions: The proposed plan strategy could represent a robust approach to account for moderate changes in target or body volume during the course of breast radiotherapy and to account for residual intrafractional respiratory motion in volumetric modulated arc therapy. The strategy, logistically simple to implement requiring only modifications to the standard planning workflow was routinely implemented at author’s institute for treatment of breast patients with RapidArc.
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