Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques. METHODS: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1-T2aN0M0) NSCLC diagnosed on the basis of 18F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was <2 cm from the chest wall) or standard radiotherapy (66 Gy in 33 daily 2 Gy fractions or 50 Gy in 20 daily 2·5 Gy fractions, depending on institutional preference) using minimisation, so no sequence was pre-generated. Clinicians, patients, and data managers had no previous knowledge of the treatment group to which patients would be assigned; however, the treatment assignment was subsequently open label (because of the nature of the interventions). The primary endpoint was time to local treatment failure (assessed according to Response Evaluation Criteria in Solid Tumors version 1.0), with the hypothesis that SABR would result in superior local control compared with standard radiotherapy. All efficacy analyses were based on the intention-to-treat analysis. Safety analyses were done on a per-protocol basis, according to treatment that the patients actually received. The trial is registered with ClinicalTrials.gov (NCT01014130) and the Australia and New Zealand Clinical Trials Registry (ACTRN12610000479000). The trial is closed to new participants. FINDINGS: Between Dec 31, 2009, and June 22, 2015, 101 eligible patients were enrolled and randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35). Five (7·6%) patients in the SABR group and two (6·5%) in the standard radiotherapy group did not receive treatment, and a further four in each group withdrew before study end. As of data cutoff (July 31, 2017), median follow-up for local treatment failure was 2·1 years (IQR 1·2-3·6) for patients randomly assigned to standard radiotherapy and 2·6 years (IQR 1·6-3·6) for patients assigned to SABR. 20 (20%) of 101 patients had progressed locally: nine (14%) of 66 patients in the SABR group and 11 (31%) of 35 patients in the standard radiotherapy group, and freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0·32, 95% CI 0·13-0·77, p=0·0077). Median time to local treatment failure was not reached in either group. In patients treated with SABR, there was one grade 4 adverse event (dyspnoea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnoea, and one fatigue) related to treatment compared with two grade 3 events (chest pain) in the standard treatment group. INTERPRETATION: In patients with inoperable peripherally located stage 1 NSCLC, compared with standard radiotherapy, SABR resulted in superior local control of the primary disease without an increase in major toxicity. The findings of this trial suggest that SABR should be the treatment of choice for this patient group. FUNDING: The Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, and the Cancer Society of New Zealand and the Cancer Research Trust New Zealand (formerly Genesis Oncology Trust).

A one-step cone-beam CT-enabled planning-to-treatment model for palliative radiotherapy-from development to implementation.

PURPOSE: To develop a cone-beam computed tomography (CT)-enabled one-step simulation-to-treatment process for the treatment of bone metastases. METHODS AND MATERIALS: A three-phase prospective study was conducted. Patients requiring palliative radiotherapy to the spine, mediastinum, or abdomen/pelvis suitable for treatment with simple beam geometry (≤2 beams) were accrued. Phase A established the accuracy of cone-beam CT images for the purpose of gross tumor target volume (GTV) definition. Phase B evaluated the feasibility of implementing the cone-beam CT-enabled planning process at the treatment unit. Phase C evaluated the online cone-beam CT-enabled process for the planning and treatment of patients requiring radiotherapy for bone metastases. RESULTS: Eighty-four patients participated in this study. Phase A (n = 9) established the adequacy of cone-beam CT images for target definition. Phase B (n = 45) established the quality of treatment plans to be adequate for clinical implementation for bone metastases. When the process was applied clinically in bone metastases (Phase C), the degree of overlap between planning computed tomography (PCT) and cone-beam CT for GTV and between PCT and cone-beam CT for treatment field was 82% ± 11% and 97% ± 4%, respectively. The oncologist's decision to accept the plan under a time-pressured environment remained of high quality, with the cone-beam CT-generated treatment plan delivering at least 90% of the prescribed dose to 100% ± 0% of the cone-beam CT planning target volume (PTV). With the assumption that the PCT PTV is the gold-standard target, the cone-beam CT-generated treatment plan delivered at least 90% and at least 95% of dose to 98% ± 2% and 97% ± 5% of the PCT PTV, respectively. The mean time for the online planning and treatment process was 32.7 ± 4.0 minutes. Patient satisfaction was high, with a trend for superior satisfaction with the cone-beam CT-enabled process. CONCLUSIONS: The cone-beam CT-enabled palliative treatment process is feasible and is ready for clinical implementation for the treatment of bone metastases using simple beam geometry, providing a streamlined one-step process toward palliative radiotherapy.

Quantifying interobserver variation in target definition in palliative radiotherapy.

PURPOSE: To describe the degree of interobserver and intraobserver variability in target and field definition when using three-dimensional (3D) volume- vs. two-dimensional (2D) field-based planning. METHODS AND MATERIALS: Standardized case scenario and diagnostic imaging for 9 palliative cases (3 bone metastases, 3 palliative lung cancer, and 3 abdominal pelvis soft-tissue disease) were presented to 5 study radiation oncologists. After a decision on what the intended anatomic target should be, observers created two sets of treatment fields, first using a 2D field-based and then a 3D volume-based planning approach. Percent overlap, under-coverage, and over-coverage were used to describe interobserver and intraobserver variations in target definition. RESULTS: The degree of interobserver variation for 2D and 3D planning was similar with a degree of overlap of 76% (range, 56%-85%) and 74% (range, 55%-88%), respectively. When comparing the treatment fields defined by the same observer using the two different planning methods, the mean degree of overlap was 78%; over-coverage, 22%; and under-coverage, 41%. There was statistically significantly more under-coverage when field-based planning was used for bone metastases (33%) vs. other anatomic sites (16%) (p = 0.02). In other words, 2D planning is more likely to result in geographic misses in bone metastases compared with other areas. CONCLUSIONS: In palliative radiotherapy clinically significant interobserver and intraobserver variation existed when using both field- and volume-based planning approaches. Strategies that would reduce this variability deserve further investigation.