Serial 4DCT/4DPET imaging to predict and monitor response for locally-advanced non-small cell lung cancer chemo-radiotherapy.

BACKGROUND AND PURPOSE: A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power. MATERIALS AND METHODS: Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan-Meier method. RESULTS: 32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p < 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival. CONCLUSIONS: Several 4DPET/CT features and rates of change can reach significant association (p < 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging.

Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Treatment of locally advanced non-small cell lung cancer with chemoradiotherapy (CRT) is limited by development of toxicity in normal tissue, including radiation esophagitis (RE). Increasingly, (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is being used for adaptive planning. Our aim was to assess changes in esophageal FDG uptake during CRT and relate the changes to the onset and severity of RE. METHODS: This prospective study in patients with stage II-III non-small cell lung cancer involved serial four-dimensional computed tomography and PET scans during CRT (60-74Gy). RE was recorded weekly using the Common Terminology Criteria for Adverse Events (v4.0), and imaging was performed at weeks 0, 2, 4, and 7. Changes in the esophagus's peak standard uptake value (SUVpeak) were analyzed for each time point and correlated with grade of RE using the Wilcoxon rank-sum test. The volume of esophagus receiving 50 Gy (V50) and volume of esophagus receiving 60 Gy (V60) were correlated with the development of RE, and the C-statistic (area under the curve [AUC]) was calculated to measure predictivity of grade 3 RE. RESULTS: RE developed in 20 of 27 patients (74%), with grade 3 reached in 6 (22%). A significant percentage increase in SUVpeak in the patients with RE was noted at week 4 (p = 0.01) and week 7 (p = 0.03). For grade 3 RE, a significant percentage increase in SUVpeak was noted at week 2 (p = 0.01) and week 7 (p = 0.03) compared with that for less than grade 3 RE. Median V50 (46.3%) and V60 (33.4%) were significantly higher in patients with RE (p = 0.04). The AUC measurements suggested that the percentage change in SUVpeak at week 2 (AUC = 0.69) and V50 (AUC = 0.67) and V60 (AUC = 0.66) were similarly predictive of grade 3 RE. CONCLUSIONS: Serial FDG-PET images during CRT show significant increases in SUVpeak for patients in whom RE develops. The changes at week 2 may predict those at risk for the development of grade 3 RE and may be informative for adaptive planning and early intervention.

Contouring variations and the role of atlas in non-small cell lung cancer radiation therapy: Analysis of a multi-institutional preclinical trial planning study.

PURPOSE: To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation. METHODS AND MATERIALS: Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases. RESULTS: Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions' plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire. CONCLUSIONS: The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial.

Capturing acute toxicity data during lung radiotherapy by using a patient-reported assessment tool.

BACKGROUND: Comprehensive and accurate assessment of symptoms experienced by patients undergoing lung radiotherapy (RT) is challenging. This study aims to evaluate the feasibility and utility of collecting acute toxicity information by using a patient-reported instrument, the Thoracic Symptom Self-Assessment Tool (TSSAT). METHODS: The TSSAT is based on the CTCAE v3.0(Common Toxicity Criteria of Adverse Events). All patients undergoing lung RT at our center from May 2008 to April 2009 were asked to complete the TSSAT on day 1 and weekly during RT. TSSAT scores were compared with clinician reporting of the same symptoms. Descriptive statistics and weighted kappa values were calculated to measure the agreement between patient- and clinician-reported acute toxicity. RESULTS: Of 300 consecutive patients approached, 49% (148/300) completed the TSSAT at least once. Patient participation and compliance were associated with treatment intent; radical (87%) vs. palliative (25%); P = <.0001. The average data completion rate by patients was 72%, and the average toxicity documentation rate by clinicians was 67%. Agreement between patients and clinicians was fair to moderate for most symptoms; the majority (>79%) of the differences were within one grade. Patients reported greater severity than clinicians for subjective symptoms. Clinicians graded greater severity than patients for the more observable symptoms. CONCLUSIONS: The TSSAT has been shown to be feasible and accepted by patients receiving radical dose RT. Patient-reported assessments may improve acute symptom management in the future.

Volumetric image guidance using carina vs spine as registration landmarks for conventionally fractionated lung radiotherapy.

PURPOSE: To compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage. METHODS AND MATERIALS: For 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumor (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration. RESULTS: Spine and carina registrations identified setup errors ≥ 5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage. CONCLUSION: Frequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.

Tumor regression and positional changes in non-small cell lung cancer during radical radiotherapy.

INTRODUCTION: We have used respiratory-correlated cone beam computed tomography (rcCBCT) imaging to study the volumetric and positional changes that occur throughout the course of radical radiotherapy in non-small cell lung cancer (NSCLC). METHODS: Tumor volumes and centers of mass were recorded and analyzed on weekly serial rcCBCT images of NSCLC patients treated with radical radiotherapy to a dose ≥45 Gy with concurrent chemotherapy. RESULTS: Sixty patients with locally advanced NSCLC were included; in 31 patients, the primary tumor was peripheral and thus suitable for contouring. There was a mean percent decrease of 40.2% by fraction 15 and 51.1% by treatment completion. Among all 60 patients, 19 patients (32%) had more than 30% regression by fraction 15 and 25 patients (81%) by treatment completion. Statistically significant tumor migration in at least one direction between the first and the last 2 weeks was demonstrated in 14 of 27 patients. Clinically relevant changes (atelectasis and effusions) were noted in 11 of 29 visually assessed patients. CONCLUSIONS: Current rcCBCT image quality allows assessment of tumors located more peripherally. Significant tumor regression was documented in the majority of patients. In view of these observations, the suitability of adaptive radiotherapy in radical lung cancer treatment should be further investigated.

Effect of image-guidance frequency on geometric accuracy and setup margins in radiotherapy for locally advanced lung cancer.

PURPOSE: To assess the relative effectiveness of five image-guidance (IG) frequencies on reducing patient positioning inaccuracies and setup margins for locally advanced lung cancer patients. METHODS AND MATERIALS: Daily cone-beam computed tomography data for 100 patients (4,237 scans) were analyzed. Subsequently, four less-than-daily IG protocols were simulated using these data (no IG, first 5-day IG, weekly IG, and alternate-day IG). The frequency and magnitude of residual setup error were determined. The less-than-daily IG protocols were compared against the daily IG, the assumed reference standard. Finally, the population-based setup margins were calculated. RESULTS: With the less-than-daily IG protocols, 20-43% of fractions incurred residual setup errors ≥ 5 mm; daily IG reduced this to 6%. With the exception of the first 5-day IG, reductions in systematic error (∑) occurred as the imaging frequency increased and only daily IG provided notable random error (σ) reductions (∑ = 1.5-2.2 mm, σ = 2.5-3.7 mm; ∑ = 1.8-2.6 mm, σ = 2.5-3.7 mm; and ∑ = 0.7-1.0 mm, σ = 1.7-2.0 mm for no IG, first 5-day IG, and daily IG, respectively. An overall significant difference in the mean setup error was present between the first 5-day IG and daily IG (p < .0001). The derived setup margins were 5-9 mm for less-than-daily IG and were 3-4 mm with daily IG. CONCLUSION: Daily cone-beam computed tomography substantially reduced the setup error and could permit setup margin reduction and lead to a reduction in normal tissue toxicity for patients undergoing conventionally fractionated lung radiotherapy. Using first 5-day cone-beam computed tomography was suboptimal for lung patients, given the inability to reduce the random error and the potential for the systematic error to increase throughout the treatment course.

10 Years Of Exposure to a Radiation Therapist Research Culture: Where Are We Now?

INTRODUCTION: Over the past 10 years, various programmatic changes have been implemented in our radiotherapy department to increase radiation therapist (RT) research activities. The aim of this qualitative study was to investigate the attitudes of RTs who have been working in a research-rich environment concerning current research activities and the presence of enablers and inhibiters. MATERIALS AND METHODS: After obtaining research ethics approval, 5 focus groups and 6 interviews were conducted with a group of 30 RTs with varying levels of clinical experience, who were currently employed in our department. Data were audiotaped, transcribed, then analyzed independently by two investigators using a thematic approach. Emerging themes and categories were captured and evaluated. RESULTS: RTs most frequently engaged in research activities from a desire for patient service improvement and professional development. The main enablers identified were a system of process support and mentorship, and access to useful research tools and databases (e.g., patient imaging databases). The most commonly noted inhibitor to research activities was securing protected research time. CONCLUSIONS: After 10 years of developing a research-rich environment, this study found that the majority of RTs were directly involved in some form of research, although the definition of research varied significantly. Enablers were identified as factors that support the practical aspects of RT research, rather than the gaining of theoretical knowledge. Although some of the inhibitors noted are similar to those working in research-naive departments, they also add the practical considerations of balancing research and clinical practice. The practical nature of both the enablers and inhibitors found in this study support the hypothesis that generating a research-rich environment for RTs has shifted their priorities from "thinking about research" to "doing research."

Investigating User Perspective on Training and Clinical Implementation of Volumetric Imaging.

PURPOSE: Volumetric imaging (VI) is gaining momentum as a clinical tool for image guidance. The purpose of this study was to explore radiation therapists' (RTs) perception of VI training and clinical implementation. The results provide an evaluation of current training for continuous improvement, identify educational needs for the future, and chart a path for higher level evaluation of the learning activities. METHODS: Sixty-five RTs who received initial training and subsequent front-end user experience with VI were contacted with an electronic posttraining questionnaire. Defined with assistance from a pilot group to encompass relevant aspects of training and VI, the survey consisted of 16 questions using a 4-point Likert scale and 1 open-ended comment box. The main sections of the survey were: demographics, current training satisfaction, user perception of competence with VI software manipulation, and assessment of future training needs for RTs. RESULTS: Forty-five returned surveys (69%) were used for analysis. Results were examined for all participants, and then separated by subgroups for comparison with the Fisher exact test. The subgroups used were years of RT experience (<2 years, 2-5 years, 6-10 years, >10 years), and length of hands-on practice with VI (<3 months, 3-6 months, 7-9 months, >9 months). There was a consensus that training was organized (93%), comprehensive (89%), and adequate for VI clinical application (91%). Although 62% of respondents were confident with soft-tissue visualization, 95% agreed with the need for further training. Proposed cross-sectional anatomy review was seen as beneficial in 73%, though analysis with subgroups (experience with VI [P = .042], experience as an RT [P = .019]) showed that less experienced staff perceived a supplemental review session valuable. A total of 93% had confidence using VI for image matching; however, subgroup analysis revealed that the more experienced RTs are less confident (P = .016). Although only 58% agreed that workflow is improved with VI, 93% felt that volumetric imaging increased accuracy of radiotherapy. Common themes for improvement of future training sessions included conducting training closer to VI unit placement, and increased hands-on use of the software complemented case studies. CONCLUSIONS: RTs felt the initial VI image training assisted them in gaining confidence in interpreting and analyzing information obtained from VI. They found this training organized, comprehensive, and adequate for their needs. Continuous training for implementation of new technology is essential to the success of image guidance methods.

Investigating Patient Wait Times for Daily Outpatient Radiotherapy Appointments (A Single-Centre Study).

INTRODUCTION: Patient satisfaction is an important indicator of quality in health care. Radiotherapy (RT) requires patients to attend daily treatment through outpatient appointments (OPA). Therefore, wait times (WT) for daily RT OPAs can have a significant impact on patient satisfaction. This study aims to quantify WTs associated with daily RT OPAs and investigate the cause of identified delays. METHODS: A total of 128 outpatients scheduled on eight different linear accelerators for RT were included in this ethics-approved study. Radiation therapists recorded the entry time (time patient entered the treatment room) for each OPA over 10 consecutive treatment days. Where applicable, radiation therapists recorded the cause for appointment delays. Subsequently, WTs were calculated as the difference between the scheduled appointment time and the entry time. Subgroup analysis by time of appointment and anatomical treatment sites was performed. RESULTS: Mean WT ± standard deviation (SD) was 7.2 ± 27 min. for 866 OPAs. A total of 382/866 (44%) OPAs were early or on time (-12 ± 21 min.); 484/866 (56%) were delayed (22 ± 20 min.). The delays were primarily attributed to an indirect cause of catching up from previous delayed appointments (73%). The WT was ≤20 min. for 693/866 OPAs (80.0%). The mean WT ± SD was longest for midday appointments (10:30 AM-2:30 PM) at 9.5 ± 29 min. and was statistically significant (P = .020). The comparison of WTs by treatments sites showed pelvis site (majority prostate cancer patients) experiencing the longest WT ± SD at 11 ± 22 min. (P < .0001), caused by specific radiotherapy treatment protocol. CONCLUSION: Most OPAs (80%) were treated within 20 min. of their scheduled time. Reported delays were influenced by clinic workflow and coordination of multiple appointments throughout the day. The findings of this study will assist in the formulation of strategies to improve efficiency and patient satisfaction.

The Influence of Programmatic Change on Radiation Therapist Research Capacity-A Single-center Case Study.

PURPOSE: To identify various programmatic changes implemented in a Canadian radiotherapy department to build therapist research capacity, and to determine their combined impact on quantitative metrics of therapist research output. METHODS AND MATERIALS: This was a single-center case study design. Programmatic changes were retrospectively identified from various departmental documentary sources. Those changes, which were active between January 2004 and December 2008 and were implemented with the intention of increasing therapist research output, were categorized by primary purpose according to published criteria from the Allied Health Professions Research and Development Action Plan. Therapist research output was collected over the same time period by an annual department-wide e-mail request for information and verified through various independent sources. RESULTS: Five educational initiatives had the potential to build therapist research knowledge and skills (e.g., journal club). Changes implemented to provide infrastructure to sustain therapist research included the creation of roles incorporating a formal research component. Four initiatives had the potential to promote research dissemination and networking (e.g., writing group). The number of therapist principal authors increased during the 5 years (from 4 to 14 per annum), with approximately 60% of articles published in international radiation medicine journals. The number of therapists presenting at conferences increased from 32 in 2004 to 63 in 2008, with 94% of submitted abstracts accepted for presentations in 2008. Therapists accumulated over $52,000 in peer-reviewed grant funds as principal investigators and the proportion of research-based therapist academic appointments has increased from 10% to 33% of appointees. CONCLUSION: Invaluable progress has been made in a Canadian radiotherapy department by combining multiple research capacity building programmatic changes to establish a culture that encourages and supports therapist research pursuits. This has increased both the quantity and quality of therapist research activity.

Cone-beam computed tomographic image guidance for lung cancer radiation therapy.

PURPOSE: To determine the geometric accuracy of lung cancer radiotherapy using daily volumetric, cone-beam CT (CBCT) image guidance and online couch position adjustment. METHODS AND MATERIALS: Initial setup accuracy using localization CBCT was analyzed in three lung cancer patient cohorts. The first (n = 19) involved patients with early-stage non-small-cell lung cancer (NSCLC) treated using stereotactic body radiotherapy (SBRT). The second (n = 48) and third groups (n = 20) involved patients with locally advanced NSCLC adjusted with manual and remote-controlled couch adjustment, respectively. For each group, the couch position was adjusted when positional discrepancies exceeded +/-3 mm in any direction, with the remote-controlled couch correcting all three directions simultaneously. Adjustment accuracy was verified with a second CBCT. Population-based setup margins were derived from systematic (Sigma) and random (sigma) positional errors for each group. RESULTS: Localization imaging demonstrates that 3D positioning errors exceeding 5 mm occur in 54.5% of all delivered fractions. CBCT reduces these errors; post-correction Sigma and sigma ranged from 1.2 to 1.9 mm for Group 1, with 82% of all fractions within +/-3 mm. For Group 2, Sigma and sigma ranged between 0.8 and 1.8 mm, with 76% of all treatment fractions within +/-3 mm. For Group 3, the remote-controlled couch raised this to 84%, and Sigma and sigma were reduced to 0.4 to 1.7 mm. For each group, the postcorrection setup margins were 4 to 6 mm, 3 to 4 mm, and 2 to 3 mm, respectively. CONCLUSIONS: Using IGRT, high geometric accuracy is achievable for NSCLC patients, potentially leading to reduced PTV margins, improved outcomes and empowering adaptive radiation therapy for lung cancer.

Comparison of spine, carina, and tumor as registration landmarks for volumetric image-guided lung radiotherapy.

PURPOSE: To assess the feasibility, reproducibility, and accuracy of volumetric lung image guidance using different thoracic landmarks for image registration. METHODS AND MATERIALS: In 30 lung patients, four independent observers conducted automated and manual image registrations on Day 1 cone-beam computed tomography data sets using the spine, carina, and tumor (720 image registrations). The image registration was timed, and the couch displacements were recorded. The intraclass correlation was used to assess reproducibility, and the Bland-Altman analysis was used to compare the automatic and manual matching methods. Tumor coverage (accuracy) was assessed through grading the tumor position after image matching against the internal target volume and planning target volume. RESULTS: The image-guided process took an average of 1 min for all techniques, with the exception of manual tumor matching, which took 4 min. Reproducibility was greatest for automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right, superoinferior, and anteroposterior directions, respectively. The Bland-Altman analysis showed no significant difference between the automatic and manual registration methods. The tumor was within the internal target volume 62% and 60% of the time and was outside the internal target volume, but within the planning target volume, 38% and 40% of the time after automatic spine and automatic carina matching, respectively. CONCLUSION: For advanced lung cancer, the spine or carina can be used equally for cone-beam computed tomography image registration without compromising target coverage. The carina was more reproducible than the spine, but additional analysis is required to confirm its validation as a tumor surrogate. Soft-tissue registration is unsuitable at present, given the limitations in contrast resolution and the high interobserver variability.

Practical considerations arising from the implementation of lung stereotactic body radiation therapy (SBRT) at a comprehensive cancer center.

INTRODUCTION: With the anticipation of improved outcomes, especially for patients with early-stage non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has been rapidly introduced into the thoracic radiation oncology community. Although at first glance lung SBRT might seem methodologically similar to conventional radiotherapy, there are important differences in its execution that require particular consideration. The objective of this paper is to highlight these and other issues to contribute to the safe and effective diffusion of lung SBRT. We discuss practical challenges that have been encountered in the implementation of lung SBRT at a single, large institution and emphasize the importance of a systematic approach to the design of lung SBRT services. METHODS: Specific technical and clinical components that were identified as being important during the development of lung SBRT at Princess Margaret Hospital are described. The clinical system that evolved from these is outlined. RESULTS: Using this clinical framework the practical topics addressed include: patient assessment, simulation and treatment planning, tumor and organ at risk delineation, trial set up before treatment, on-line image-guidance, and patient follow-up. CONCLUSIONS: The potential gain in therapeutic ratio that is theoretically possible with lung SBRT can only be realized if the tumor is adequately irradiated and normal tissue spared. A discussion of the component parts of lung SBRT is presented. It is a complex process and specific challenges need to be overcome to effect the satisfactory transition of lung SBRT into routine practice.