There is evidence in some solid tumors that textural features of tumoral uptake in 18 F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Methods: Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment 18 F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Results: Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P 5 0.004) and higher contrast (mean, 0.11 vs. 0.044; P 5 0.002) and busyness (mean, 0.76 vs. 0.37; P 5 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P 5 0.003; 12.6 vs. 25.8 mo, P 5 0.002; and 12.9 vs. 20.5 mo, P 5 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P 5 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P 5 0.015, and median not reached vs. 24 mo, P 5 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P 5 0.01, and median not reached vs. 24 mo, P 5 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. Conclusion: In NSCLC, baseline 18 F-FDG PET scan uptake showing abnormal texture as measured by coarseness, contrast, and busyness is associated with nonresponse to chemoradiotherapy by RECIST and with poorer prognosis. Measurement of tumor metabolic heterogeneity with these parameters may provide indices that can be used to stratify patients in clinical trials for lung cancer chemoradiotherapy.

Respiratory motion causes errors when planning and delivering radiotherapy treatment to lung cancer patients. To reduce these errors, methods of acquiring and using four-dimensional computed tomography (4DCT) datasets have been developed. We have developed a novel method of constructing computational motion models from 4DCT. The motion models attempt to describe an average respiratory cycle, which reduces the effects of variation between different cycles. They require substantially less memory than a 4DCT dataset, are continuous in space and time, and facilitate automatic target propagation and combining of doses over the respiratory cycle. The motion models are constructed from CT data acquired in cine mode while the patient is free breathing (free breathing CT - FBCT). A "slab" of data is acquired at each couch position, with 3-4 contiguous slabs being acquired per patient. For each slab a sequence of 20 or 30 volumes was acquired over 20 seconds. A respiratory signal is simultaneously recorded in order to calculate the position in the respiratory cycle for each FBCT. Additionally, a high quality reference CT volume is acquired at breath hold. The reference volume is nonrigidly registered to each of the FBCT volumes. A motion model is then constructed for each slab by temporally fitting the nonrigid registration results. The value of each of the registration parameters is related to the position in the respiratory cycle by fitting an approximating B spline to the registration results. As an approximating function is used, and the data is acquired over several respiratory cycles, the function should model an average respiratory cycle. This can then be used to calculate the value of each degree of freedom at any desired position in the respiratory cycle. The resulting nonrigid transformation will deform the reference volume to predict the contents of the slab at the desired position in the respiratory cycle. The slab model predictions are then concatenated to produce a combined prediction over the entire region of interest. We have performed a number of experiments to assess the accuracy of the nonrigid registration results and the motion model predictions. The individual slab models were evaluated by expert visual assessment and the tracking of easily identifiable anatomical points. The combined models were evaluated by calculating the discontinuities between the transformations at the slab boundaries. The experiments were performed on five patients with a total of 18 slabs between them. For the point tracking experiments, the mean distance between where a clinician manually identified a point and where the registration results located the point, the target registration error (TRE), was 1.3 mm. The mean distance between a manually identified point and the models prediction of the point's location, the target model error (TME), was 1.6 mm. The mean discontinuity between model predictions at the slab boundaries, the Continuity Error, was 2.2 mm. The results show that the motion models perform with a level of accur...

Respiratory organ motion has a significant impact on the planning and delivery of radiotherapy (RT) treatment for lung cancer. Currently widespread techniques, such as 4D-computed tomography (4DCT), cannot be used to measure variability of this motion from one cycle to the next. In this paper, we describe the use of fast magnetic resonance imaging (MRI) techniques to investigate the intra- and inter-cycle reproducibility of respiratory motion and also to estimate the level of errors that may be introduced into treatment delivery by using various breath-hold imaging strategies during lung RT planning. A reference model of respiratory motion is formed to enable comparison of different breathing cycles at any arbitrary position in the respiratory cycle. This is constructed by using free-breathing images from the inhale phase of a single breathing cycle, then co-registering the images, and thereby tracking landmarks. This reference model is then compared to alternative models constructed from images acquired during the exhale phase of the same cycle and the inhale phase of a subsequent cycle, to assess intra- and inter-cycle variability ('hysteresis' and 'reproducibility') of organ motion. The reference model is also compared to a series of models formed from breath-hold data at exhale and inhale. Evaluation of these models is carried out on data from ten healthy volunteers and five lung cancer patients. Free-breathing models show good levels of intra- and inter-cycle reproducibility across the tidal breathing range. Mean intra-cycle errors in the position of organ surface landmarks of 1.5(1.4)-3.5(3.3) mm for volunteers and 2.8(1.8)-5.2(5.2) mm for patients. Equivalent measures of inter-cycle variability across this range are 1.7(1.0)-3.9(3.3) mm for volunteers and 2.8(1.8)-3.3(2.2) mm for patients. As expected, models based on breath-hold sequences do not represent normal tidal motion as well as those based on free-breathing data, with mean errors of 4.4(2.2)-7.7(3.9) mm for volunteers and 10.1(6.1)-12.5(6.3) mm for patients. Errors are generally larger still when using a single breath-hold image at either exhale or inhale to represent the lung. This indicates that account should be taken of intra- and inter-cycle respiratory motion variability and that breath-hold-based methods of obtaining data for RT planning may potentially introduce large errors. This approach to analysis of motion and variability has potential to inform decisions about treatment margins and optimize RT planning.

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

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