Shahreen Ahmad

Are Pretreatment 18F-FDG PET Tumor Textural Features in Non–Small Cell Lung Cancer Associated with Response and Survival After Chemoradiotherapy?

There is evidence in some solid tumors that textural features of tumoral uptake in 18F-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 18F-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 = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 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 = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 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 = 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 = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. Conclusion: In NSCLC, baseline 18F-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.

A Brief Report on the Safety Study of Induction Chemotherapy Followed by Synchronous Radiotherapy and Cetuximab in Stage III Non-small Cell Lung Cancer (NSCLC): SCRATCH Study

Background: In patients with advanced (stage IIIb/IV) NSCLC, the addition of cetuximab to chemotherapy has demonstrated increased activity compared with chemotherapy alone. Furthermore, the additio of cetuximab to RT in patients with locally advanced squamous cell head & neck carcinoma significantly prolongs the duration of locoregional control and median overall survival compared to radiotherapy alone. Therefore, the SCRATCH study was designed to assess the safety of synchronous cetuximab with radical RT in patients with Stage III NSCLC. The safety results of cohort 1 from this phase I study are presented below. Methods: Twelve patients with inoperable stage III NSCLC were enrolled into cohort I. Inclusion criteria were performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria were previous malignancy, thoracic RT or treatment with EGFR (epidermal growth factor receptor) targeted therapy. Patients received platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250mg/m2) and concomitant Rt (64Gy/32fractions/45days). The primary end-point was toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments were preformed weekly during radiotherapy, and at regular follow-up visits. Results: 9 out of 12 patients coompleted the concomitant therapy as planned, with no dose reductions. 3 patients did not complete the full schedule. One died from bronchopneumonia mid-treatment; one experienced grade 3 lethargy following the first cetuximab dose and declined further cetuximab; one experienced a grade 2 skin reaction following the third dose of cetuximab and declined futher treatment. On follow-up only one patient has developed a grade III reaction – pneumonitis – which settled on steroids with intermittent oxygen. Three patients have died on follow-up (2 from disease progression and one from thromboembolic disease). Of the 12 patients entered ito the study, 8 have survived at least 1 year, measured from the first day of induction chemotherapy. Conclusion: The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable.

Inter-fraction variations in respiratory motion models

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.

Assessment of two novel ventilatory surrogates for use in the delivery of gated/tracked radiotherapy for non-small cell lung cancer

BACKGROUND In selected patients with NSCLC the therapeutic index of radical radiotherapy can be improved with gating/tracking technology. Both techniques require real-time information on target location. This is often derived from a surrogate ventilatory signal. We assessed the correlation of two novel surrogate ventilatory signals with a spirometer-derived signal. The novel signals were obtained using the VisionRT stereoscopic camera system. The VisionRT-Tracked-Point (VRT-TP) signal was derived from tracking a point located midway between the umbilicus and xiphisternum. The VisionRT-Surface-Derived-Volume (VRT-SDV) signal was derived from 3D body surface imaging of the torso. Both have potential advantages over the current surrogate signals. METHODS Eleven subjects with NSCLC were recruited. Each was positioned as for radiotherapy treatment, and then instructed to breathe in five different modes: normal, abdominal, thoracic, deep and shallow breathing. Synchronous ventilatory signals were recorded for later analysis. The signals were analysed for correlation across all modes of breathing, and phase shifts. The VRT-SDV was also assessed for its ability to determine the mode of breathing. RESULTS Both novel respiratory signals showed good correlation (r>0.80) with spirometry in 9 of 11 subjects. For all subjects the correlation with spirometry was better for the VRT-SDV signal than for the VRT-TP signal. Only one subject displayed a phase shift between the VisionRT-derived signals and spirometry. The VRT-SDV signal could also differentiate between different modes of breathing. Unlike the spirometer-derived signal, neither VisionRT-derived signal was subject to drift. CONCLUSION Both the VRT-TP and VRT-SDV signals have potential applications in ventilatory-gated and tracked radiotherapy. They can also be used as a signal for sorting 4DCT images, and to drive 4DCT single- and multiple-parameter motion models.

Building motion models of lung tumours from cone-beam CT for radiotherapy applications

A method is presented to build a surrogate-driven motion model of a lung tumour from a cone-beam CT scan, which does not require markers. By monitoring an external surrogate in real time, it is envisaged that the motion model be used to drive gated or tracked treatments. The motion model would be built immediately before each fraction of treatment and can account for inter-fraction variation. The method could also provide a better assessment of tumour shape and motion prior to delivery of each fraction of stereotactic ablative radiotherapy. The two-step method involves enhancing the tumour region in the projections, and then fitting the surrogate-driven motion model. On simulated data, the mean absolute error was reduced to 1 mm. For patient data, errors were determined by comparing estimated and clinically identified tumour positions in the projections, scaled to mm at the isocentre. Averaged over all used scans, the mean absolute error was under 2.5 mm in superior-inferior and transverse directions.

A comparison of internal target volume definition by limited four-dimensional computed tomography, the addition of patient-specific margins, or the addition of generic margins when planning radical radiotherapy for lymph node-positive non-small cell lung cancer

AIMS Radical radiotherapy for stage II/III non-small cell lung cancer (NSCLC) includes the primary tumour and positive mediastinal lymph nodes in the clinical target volume (CTV). These move independently of each other in magnitude and direction during respiration. To prevent a geographical miss, a generic margin is usually added to the CTV to create an internal target volume (ITV). Previous studies have investigated the use of additional breath-hold computed tomography to generate patient-specific ITVs for primary tumours alone. We used a similar technique to investigate the generation of patient-specific and generic ITVs for CTVs that include mediastinal lymph nodes. MATERIALS AND METHODS Thirteen patients with node-positive NSCLC had two limited end-tidal breath-hold computed tomography scans in addition to their planning computed tomography. The CTV was segmented in each scan and a rigid registration was carried out on the vertebral columns to align them. Different methods for generating an ITV were then analysed. RESULTS Generic margins provided >95% mean coverage of the reference ITV. However, with the exception of 1cm expansion margins, there were cases of inadequate coverage (<95%) for each ITV. With increasing ITV margins there was a small increase in reference ITV coverage, but at the expense of a large increase in the volume of normal tissue within the ITV. DISCUSSION For stage II/III NSCLC, ITV generation by the addition of a generic margin is not optimal. It can result in both geographical miss and excessive irradiation of normal tissue in the same treatment plan. A simple method for producing a patient-specific ITV is to co-register end-tidal breath-hold computed tomography scans to the planning scan. CONCLUSIONS Further work is required to determine whether end-tidal breath-hold scans are representative of the anatomy at the limits of tidal respiration. Planning strategies are also needed to account for breathing cycle variation during a course of radiotherapy.

TH‐D‐332‐07: Removing Artifacts From 4DCT Volumes Acquired in Cine Mode Using B‐Spline Non‐Rigid Registrations

Purpose: To remove artefacts that occur between adjacent couch positions in 4DCT volumes acquired in Cine mode. Method and Materials: separate B‐spline non‐rigid registration is performed between an artefact free reference volume and the data from each individual couch position in the 4DCT volume. The registration is performed using an extended control point grid that covers all of the couch positions and is common to all of the registrations. Therefore the result of each registration defines a transformation over all couch positions but was only constrained by data from one couch position. The registration results from all couch position are then combined into a single B‐spline transformation. The control point displacements in the combined transformation are a weighted average of the displacements in the individual registrations. The weight for each registration is different for each row in the control point grid, and depends on the contribution that the control points make to the transformation in the region of the couch position that was registered. The combined transformation is continuous across all the couch positions, and when used to deform the reference volume will produce an artefact free prediction of the anatomy in the same respiratory state as the original 4DCT volume. Results: This method has been applied to 4DCT data from five patients that were subject to artefacts between couch positions. In all cases our method produced volumes that resembled the original 4DCT data but were free of artefacts between adjacent couch positions. Conclusion: We have presented a novel method based on B‐spline non‐rigid registration that can remove the artefacts that occur between adjacent couch positions in 4DCT volumes acquired in Cine model, and have successfully demonstrated this method on data from five patients.

Fully-deformable patient motion models from cone-beam CT for radiotherapy applications

We propose a method to build a fully deformable motion model directly from cone-beam CT (CBCT) projections. This allows inter-fraction variations in the respiratory motion to be accounted for. It is envisaged that the model be used to track the tumour, and monitor organs at risk (OAR), during gated or tracked radiotherapy (RT) treatment of lung cancer. The method is tested on CBCT projections from a simulated phantom in two cases. The simulations are generated from a patient respiratory trace and associated CBCT scanner geometry. Without and with motion correction, l2 norm maximum errors were reduced from 24.5 to 0.698 mm in case 1, and 20.0 to 0.101 mm in case 2, respectively.