Use of CD-ROM-based tool for analyzing contouring variations in involved-field radiotherapy for Stage III NSCLC.

BACKGROUND: Interclinician variability in defining target volumes is a problem in conformal radiotherapy. A CD-ROM-based contouring tool was used to conduct a dummy run in an international trial of involved-field chemoradiotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: The CT scan of an eligible patient was installed on an "auto-run" CD-ROM incorporating a contouring program based on ImageJ for Windows, which runs on any personal computer equipped with a CD-ROM drive. This tool was initially piloted at four academic centers and was subsequently mailed, together with all relevant clinical, radiologic, and positron emission tomography findings, to all participating centers in the international trial. Clinicians were instructed to contour separate gross tumor volumes (GTVs) for the tumor and two enlarged nodes and a clinical target volume for the hilus. A reference "consensus" target volume for each target was jointly generated by three other clinicians. RESULTS: The data received from the four academic centers and 16 study participants were suitable for analysis. Data from one center was unsuitable for detailed analysis because the target volumes were contoured at 1.2-cm intervals. GTVs were available for a total of 21 tumors and 19 nodes, and 15 hilar clinical target volumes were available. The mean GTV of the primary tumor was 13.6 cm(3) (SD, 5.2; median, 12.3; range, 8.3-26.9). The variation in the center of the mass relative to the mean center of the mass in the left-right, ventrodorsal, and craniocaudal axes was 1.5, 0.4, and 1.0 mm, respectively. The largest volume variation was observed for the right hilar clinical target volume (mean, 33.7 cm(3); SD, 31.2; median, 20.3; range, 4.8-109.9). Smaller variations were observed for the subcarinal node (mean, GTV, 1.9 cm(3); SD, 1.2; median, 1.7; range, 0.5-5.3), except caudally where the node was difficult to distinguish from the pericardium. The "consensus" volumes for all targets were generally close to the median of the contoured values. CONCLUSION: Most clinicians were able to use this CD-ROM tool to contour target volumes in compliance with the study protocol. The rapid completion of the dummy run indicated the suitability of this approach for quality assurance in multicenter clinical trials. Routine use of similar tools will reduce the risk that new techniques (or study objectives) are misunderstood and/or misapplied in clinical trials.

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy.

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.

Can errors in reconstructing pre-chemotherapy target volumes contribute to the inferiority of sequential chemoradiation in stage III non-small cell lung cancer (NSCLC)?

Concurrent chemo-radiotherapy (CT-RT) has been shown to be superior to sequential CT-RT for stage III non-small cell lung cancer (NSCLC). Pre-chemotherapy gross tumor volumes (GTV) are commonly contoured for sequential CT-RT and, as significant inter-clinician variability exists in defining GTV's for lung cancer, we postulated that the poorer local control observed with sequential CT-RT may partly be due to the larger errors in defining GTV after chemotherapy-induced tumor regression. Pre-and post-chemotherapy CT scans for RT planning (RTP) were performed in ten patients who received induction chemotherapy for NSCLC. Image registration of pre- and post-chemotherapy RTP scans was performed for all patients. GTV's were first contoured in the conventional manner by two clinicians, i.e. by visual reconstruction from hard copies of the pre-chemotherapy diagnostic CT scans ('GTV-visual'). A 'GTV-match' was then contoured after image-registration, and the 'gold standard' volume was considered to be the overlap of the 'GTV-match' generated by both clinicians. The 'GTV-match' was on average 31-40% larger than 'GTV-visual'. The mean percentage of the 'gold standard', which was not covered by the 'GTV-visual' was similar for both clinicians, i.e. 26.3+/-12.5 and 28.0+/-15.0%. The inter-clinician agreement in contouring improved after image registration. These data suggest that conventional visual contouring of pre-chemotherapy GTV's may fail to treat the actual pre-chemotherapy tumor volume, and thus confound studies evaluating optimal sequencing of chemo-radiotherapy in NSCLC.