[en] To quantitatively evaluate dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer. Overall, 11 lung SBRT patients (8 female and 3 male; mean age: 75.0 years) with medially located tumors were included. Treatment plans with simulated rotational offsets of 1°, 3°, and 5° in roll, yaw, and pitch were generated and compared with the original plans. Both clockwise and counterclockwise rotations were investigated. The following dosimetric metrics were quantitatively evaluated: planning target volume coverage (PTV V_100%), max PTV dose (PTV D_max), percentage prescription dose to 0.35 cc of cord (cord D_0.35cc), percentage prescription dose to 0.35 cc and 5 cc of esophagus (esophagus D_0.35cc and D_5cc), and volume of the lungs receiving at least 20 Gy (lung V₂₀). Statistical significance was tested using Wilcoxon signed rank test at the significance level of 0.05. Overall, small differences were found in all dosimetric matrices at all rotational offsets: 95.6% of differences were < 1% or < 1 Gy. Of all rotational offsets, largest change in PTV V_100%, PTV D_max, cord D_0.35cc, esophagus D_0.35cc, esophagus D_5cc, and lung V₂₀ was − 8.36%, − 6.06%, 11.96%, 8.66%, 6.02%, and − 0.69%, respectively. No significant correlation was found between any dosimetric change and tumor-to-cord/esophagus distances (R² range: 0 to 0.44). Larger dosimetric changes and intersubject variations were observed at larger rotational offsets. Small dosimetric differences were found owing to rotational offsets up to 5° in lung SBRT for medially located tumors. Larger intersubject variations were observed at larger rotational offsets

[en] The purpose of this research was to study the sensitivity of Computed Tomography (CT) radiomic features to motion blurring and signal-to-noise ratios (SNR), and investigate its downstream effect regarding the classification of non-small cell lung cancer (NSCLC) histology.

Forty-three radiomic features were considered and classified into one of four categories: Morphological, Intensity, Fine Texture, and Coarse Texture. First, a series of simulations were used to study feature-sensitivity to changes in spatial-temporal resolution. A dynamic digital phantom was used to generate images with different breathing amplitudes and SNR, from which features were extracted and characterized relative to initial simulation conditions. Stage I NSCLC patients were then retrospectively identified, from which three different acquisition-specific feature-spaces were generated based on free-breathing (FB), average-intensity-projection (AIP), and end-of-exhalation (EOE) CT images. These feature-spaces were derived to cover a wide range of spatial-temporal tradeoff. Normalized percent differences and concordance correlation coefficients (CCC) were used to assess the variability between the 3D and 4D acquisition techniques. Subsequently, three corresponding acquisition-specific logistic regression models were developed to classify lung tumor histology. Classification performance was compared between the different data-dependent models.

Simulation results demonstrated strong linear dependences (p  >  0.95) between respiratory motion and morphological features, as well as between SNR and texture features. The feature Short Run Emphasis was found to be particularly stable to both motion blurring and changes in SNR. When comparing FB-to-EOE, 37% of features demonstrated high CCC agreement (CCC  >  0.8), compared to only 30% for FB-to-AIP. In classifying tumor histology, EoE images achieved an average AUC, Accuracy, Sensitivity, and Specificity of , respectively. FB images achieved respective values of , and AIP images achieved respective values of .

Several radiomic features have been identified as being relatively robust to spatial-temporal variations based on both simulation data and patient data. In general, features that were sensitive to motion blurring were not necessarily the same features that were sensitive to changes in SNR. Our modeling results suggest that the EoE phase of a 4DCT acquisition may provide useful radiomic information, particularly for features that are highly sensitive to respiratory motion. (paper)

[en] Purpose: To analyze local-regional patterns of failure after surgical resection of non-small-cell lung cancer (NSCLC). Methods and Materials: This retrospective analysis included 61 patients who underwent resection of NSCLC at Duke University Medical Center. Inclusion into the study required the following: margin-negative resection, no neoadjuvant/adjuvant radiation therapy (RT), first recurrence involving a local-regional site, and imaging studies available for review. Sites of intrathoracic disease recurrence were documented. Diagrams were constructed that illustrated sites of failure on the basis of lobe of primary tumor. Failure rates were compared by application of a two-tailed Fisher's exact test. Results: All patients had CT imaging for review, and 54% also had PET imaging. The median number of local-regional recurrent sites was two (range, 1-6). For all patients, the most common site of failure was the bronchial stump/staple line (44%), which was present more often in those who had a wedge resection than in those who had a more radical procedure (79% vs. 34%, p = 0.005). Patients with initial nodal involvement (pN1-2) were not more likely to have involvement of the mediastinum than were patients with pN0 disease (64% vs. 72%, p = 0.72), but were more likely to have involvement of the supraclavicular fossa (27% vs. 4%, p = 0.04). Mediastinal involvement, without overt evidence of hilar involvement, occurred in 59% of patients. Left-sided tumors tended to involve the contralateral mediastinum more frequently than did right-sided tumors. Patterns of failure after resection are diagrammed and follow a fairly predictable pattern on the basis of involved lobe. Conclusions: These data may help clinicians construct postoperative RT volumes that are smaller than ones traditionally utilized, which may improve the therapeutic ratio

[en] Hyperpolarized (HP) ¹²⁹Xe MRI is an emerging technology that affords a non-invasive, quantitative 3D-mapping of pulmonary function. Hyperpolarization enhances the ¹²⁹Xe signal ~100,000-fold to enable imaging its 3D distribution in a single breath-hold. Moreover, ¹²⁹Xe is tissue-soluble and freely diffuses from the alveolar space into the interstitial barrier, from which it diffuses into the capillary red blood cells (RBCs). It can be separately quantified in these three compartments by virtue of its unique MRI signal frequency in each. These properties make HP ¹²⁹Xe MRI uniquely applicable to imaging modality in the management of patients with lung cancer.

[en] Purpose: To create, on the basis of available data, a mathematical model to describe the tumor stage- and field size-dependent risks/benefits of postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC), and to assess whether this simple model can accurately describe the reported changes in overall survival. Methods and Materials: The increase in overall survival afforded by PORT is assumed equal to the increase in cancer-specific survival minus the rate of RT-induced mortality. The increase in cancer-specific survival is the product of the probabilities of (residual local disease) x (sterilization of residual disease with PORT) x (absence of metastatic disease). Data were extracted from the literature to estimate these probabilities. Different models were considered to relate the RT-induced mortality to field size. Results: The rate of RT-induced mortality seems to be proportional to the cube of the field size. When these mortality rates are included in the model, the predicted changes in overall survival approximate the literature values. Conclusion: Clinical data can be explained by a simple model that suggests that RT-induced mortality is strongly dependent on field size and at least partly offsets the benefit afforded by PORT. Smaller RT fields, tailored to treat the areas most at risk for recurrence, provide the highest therapeutic ratio. The data used do not reflect the impact of chemotherapy, which will reduce the rate of distant metastases and enhance the efficacy of RT

[en] The purpose of this work was to investigate the potential relationship between radiomic features extracted from pre-treatment x-ray CT images and clinical outcomes following stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC).

Seventy patients who received SBRT for stage-1 NSCLC were retrospectively identified. The tumor was contoured on pre-treatment free-breathing CT images, from which 43 quantitative radiomic features were extracted to collectively capture tumor morphology, intensity, fine-texture, and coarse-texture. Treatment failure was defined based on cancer recurrence, local cancer recurrence, and non-local cancer recurrence following SBRT. The univariate association between each radiomic feature and each clinical endpoint was analyzed using Welch’s t-test, and p-values were corrected for multiple hypothesis testing. Multivariate associations were based on regularized logistic regression with a singular value decomposition to reduce the dimensionality of the radiomics data.

Two features demonstrated a statistically significant association with local failure: Homogeneity2 (p  =  0.022) and Long-Run-High-Gray-Level-Emphasis (p  =  0.048). These results indicate that relatively dense tumors with a homogenous coarse texture might be linked to higher rates of local recurrence. Multivariable logistic regression models produced maximum values of , and , for the recurrence, local recurrence, and non-local recurrence endpoints, respectively.

The CT-based radiomic features used in this study may be more associated with local failure than non-local failure following SBRT for stage I NSCLC. This finding is supported by both univariate and multivariate analyses. (paper)

[en] Purpose: To quantify uncertainties in delineating an internal target volume (ITV) and to understand how these uncertainties may be individually minimized for stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC). Methods and Materials: Twenty patients with NSCLC who were undergoing SBRT were imaged with free-breathing 3-dimensional computed tomography (3DCT) and 10-phase 4-dimensional CT (4DCT) for delineating gross tumor volume (GTV)_3D and ITV_10Phase (ITV3). The maximum intensity projection (MIP) CT was also calculated from 10-phase 4DCT for contouring ITV_MIP (ITV1). Then, ITV_COMB (ITV2), ITV_{10Phase+GTV3D} (ITV4), and ITV_{10Phase+ITVCOMB} (ITV5) were generated by combining ITV_MIP and GTV_3D, ITV_10phase and GTV_3D, and ITV_10phase and ITV_COMB, respectively. All 6 volumes (GTV_3D and ITV1 to ITV5) were delineated in the same lung window by the same radiation oncologist. The percentage of volume difference (PVD) between any 2 different volumes was determined and was correlated to effective tumor diameter (ETD), tumor motion ranges, R_3D, and the amplitude variability of the recorded breathing signal (v) to assess their volume variations. Results: The mean (range) tumor motion (R_SI, R_AP, R_ML, and R_3D) and breathing variability (v) were 7.6 mm (2-18 mm), 4.0 mm (2-8 mm), 3.3 mm (0-7.5 mm), 9.9 mm (4.1-18.7 mm), and 0.17 (0.07-0.37), respectively. The trend of volume variation was GTV_3D < ITV1 < ITV2 ≈ ITV3 < ITV4 < ITV5. The means ± SDs of these volumes were 11.1 ± 9.3 cc, 13.2 ± 10.5 cc, 14.9 ± 11.0 cc, 14.7 ± 11.4 cc, 15.9 ± 11.7 cc, and 16.4 ± 11.8 cc, respectively. All comparisons between the target volumes showed statistical significance (P≤.001), except for ITV2 and ITV3 (P=.594). The PVDs for all volume pairs correlated negatively with ETD (r≤−0.658, P≤.006) and positively with R_3D (r≥0.503, P≤.047). The PVDs for pairs of ITV2 vs ITV5 and ITV5 vs ITV4 negatively correlated with ETD (r=0.502, −0.626; P=.047, .010). No other correlation was found. Conclusion: Uncertainties in individualized ITVs for SBRT of early stage NSCLC could effectively be minimized by combining information from 3DCT, 4DCT, and MIP. If these images cannot be efficiently contoured, a combination of ITV_MIP and GTV_3D could be an effective alternative.

[en] To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response

[en] To develop guidelines for the work-up and radiation therapy (RT) management of patients with plasma cell neoplasms.

[en] Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.