Correlation of normal lung density changes with dose after stereotactic body radiotherapy (SBRT) for early stage lung cancer.

BACKGROUND AND PURPOSE: To investigate the correlation between normal lung CT density changes with dose accuracy and outcome after stereotactic body radiation therapy (SBRT) for patients with early stage non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-one patients (with a total of 33 lesions) with non-small cell lung cancer were selected out of 270 patients treated with SBRT at a single institution between 2003 and 2009. Out of these 31 patients, 10 patients had developed radiation pneumonitis (RP). Dose distributions originally planned using a 1-D pencil beam-based dose algorithm were retrospectively recomputed using different algorithms. Prescription dose was 48 Gy in 4 fractions in most patients. Planning CT images were rigidly registered to follow-up CT datasets at 3-9 months after treatment. Corresponding dose distributions were mapped from planning to follow-up CT images. Hounsfield Unit (HU) changes in lung density in individual, 5 Gy, dose bins from 5 to 45 Gy were assessed in the peri-tumoral region. Correlations between HU changes in various normal lung regions, dose indices (V20, MLD, generalized equivalent uniform dose (gEUD)), and RP grade were investigated. RESULTS: Strong positive correlation was found between HU changes in the peri-tumoral region and RP grade (Spearman's r = 0.760; p < 0.001). Positive correlation was also observed between RP and HU changes in the region covered by V20 for all algorithms (Spearman's r ≥ 0.738; p < 0.001). Additionally, V20, MLD, and gEUD were significantly correlated with RP grade (p < 0.01). MLD in the peri-tumoral region computed with model-based algorithms was 5-7% lower than the PB-based methods. CONCLUSION: Changes of lung density in the peri-tumoral lung and in the region covered by V20 were strongly associated with RP grade. Relative to model-based methods, PB algorithms over-estimated mean peri-tumoral dose and showed displacement of the high-dose region, which correlated with HU changes on follow-up CT scans.

Application of radiomics for the prediction of HPV status for patients with head and neck cancers.

PURPOSE: To perform radiomic analysis of primary tumors extracted from pretreatment contrast-enhanced computed tomography (CE-CT) images for patients with oropharyngeal cancers to identify discriminant features and construct an optimal classifier for the characterization and prediction of human papilloma virus (HPV) status. MATERIALS AND METHODS: One hundred and eighty seven patients with oropharyngeal cancers with known HPV status (confirmed by immunohistochemistry-p16 protein testing) were retrospectively studied as follows: Group A: 95 patients (19HPV- and 76HPV+) from the MICAII grand challenge. Group B: 92 patients (52HPV- and 40HPV+) from our institution. Radiomic features (172) were extracted from pretreatment diagnostic CE-CT images of the gross tumor volume (GTV). Levene and Kolmogorov-Smirnov's tests with absolute biserial correlation (>0.48) were used to identify the discriminant features between the HPV+ and HPV- groups. The discriminant features were used to train and test eight different classifiers. Area under receiver operating characteristic (AUC), positive predictive and negative predictive values (PPV and NPV, respectively) were used to evaluate the performance of the classifiers. Principal component analysis (PCA) was applied on the discriminant feature set and seven PCs were used to train and test a generalized linear model (GLM) classifier. RESULTS: Among 172 radiomic features only 12 radiomic features (from 3 categories) were significantly different (P < 0.05, |BSC| > 0.48) between the HPV+ and HPV- groups. Among the eight classifiers trained and applied for prediction of HPV status, the GLM showed the highest performance for each discriminant feature and the combined 12 features: AUC/PPV/NPV = 0.878/0.834/0.811. The GLM high prediction power was AUC/PPV/NPV = 0.849/0.731/0.788 and AUC/PPV/NPV = 0.869/0.807/0.870 for unseen test datasets for groups A and B, respectively. After eliminating the correlation among discriminant features by applying PCA analysis, the performance of the GLM was improved by 3.3%, 2.2%, and 1.8% for AUC, PPV, and NPV, respectively. CONCLUSIONS: Results imply that GTV's for HPV+ patients exhibit higher intensities, smaller lesion size, greater sphericity/roundness, and higher spatial intensity-variation/heterogeneity. Results are suggestive that radiomic features primarily associated with the spatial arrangement and morphological appearance of the tumor on contrast-enhanced diagnostic CT datasets may be potentially used for classification of HPV status.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

To gate or not to gate - dosimetric evaluation comparing Gated vs. ITV-based methodologies in stereotactic ablative body radiotherapy (SABR) treatment of lung cancer.

BACKGROUND: To compare retrospectively generated gated plans to conventional internal target volume (ITV)-based plans and to evaluate whether gated radiotherapy provides clinically relevant dosimetric improvements to organs-at-risk (OARs). METHODS: Evaluation was performed of 150 stereotactic ablative radiotherapy treatment plans delivered to 128 early-stage (T1-T3 (<5 cm)) NSCLC patients. To generate gated plans, original ITV-based plans were re-optimized and re-calculated on the end-exhale phase and using gated planning target volumes (PTV). Gated and ITV-based plans were produced for 3 × 18 Gy and 4 × 12 Gy fractionation regimens. Dose differences between gated and ITV-based plans were analyzed as a function of both three-dimensional motion and tumor volume. OARs were analyzed using RTOG and AAPM dose constraints. RESULTS: Differences between gated and ITV-based plans for all OAR indices were largest for the 3 × 18 Gy regimen. For this regimen, MLD differences calculated by subtracting the gated values from the ITV-based values (ITV vs. Gated) were 0.10 ± 0.56 Gy for peripheral island (N = 57), 0.16 ± 0.64 Gy for peripheral lung-wall seated (N = 57), and 0.10 ± 0.64 Gy for central tumors (N = 36). Variations in V20 were similarly low, with the greatest differences occurring in peripheral tumors (0.20 ± 1.17 %). Additionally, average differences (in 2Gy-equivalence) between ITV and gated lung indices fell well below clinical tolerance values for all fractionation regimens, with no clinically meaningful differences observed from the 4 × 12 Gy regimen and rarely for the 3 × 18 Gy regimen (<2 % of cases). Dosimetric differences between gated and ITV-based methods did generally increase with increasing tumor motion and decreasing tumor volume. Dose to ribs and bronchial tree were slightly higher in gated plans compared to ITV-based plans and slightly lower for esophagus, heart, spinal cord, and trachea. CONCLUSIONS: Analysis of 150 SABR-based lung cancer treatment plans did not show a substantial benefit for the gating regimen when compared to ITV-based treatment plans. Small benefits were observed only for the largest tumor motion (exceeding 2 cm) and the high dose treatment regimen (3 × 18 Gy), though these benefits did not appear to be clinically relevant.

Hyperfine suppression of 2 3 S 1--3 3 P J transitions in 3He.

Two anomalously weak transitions within the 2(3)S_(1)--3(3)P_(J) manifolds in 3He have been identified. Their transition strengths are measured to be 1000 times weaker than that of the strongest transition in the same group. This dramatic suppression of transition strengths is due to the dominance of the hyperfine interaction over the fine-structure interaction. An alternative selection rule based on IS coupling (where the nuclear spin is first coupled to the total electron spin) is proposed. This provides qualitative understanding of the transition strengths. It is shown that the small deviations from the IS coupling model are fully accounted for by an exact diagonalization of the strongly interacting states.