BACKGROUND: Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT).
METHODS: This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR.
DISCUSSION: This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.
BACKGROUND: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.
METHODS: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided a of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.
FINDINGS: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.
INTERPRETATION: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.
FUNDING: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
Objectives: Palliative thoracic radiotherapy (RT) can improve quality of life for patients with advanced lung cancer, but treatment can be associated with acute toxicity and symptomatic relief may take several weeks. The optimal fractionation schedule is not known. Delivery of RT near the end of life (EOL) is an emerging indicator of poor quality care. The aim of this study was to determine utilization of palliative thoracic RT in the last 4 weeks of life, and factors associated with its use, in patients with incurable lung cancer in a population-based healthcare system.
Materials and Methods: All patients with lung cancer in British Columbia treated with palliative thoracic RT in 2014 and 2015 were identified. Associations between starting a course of palliative thoracic RT within 4 weeks of death and patient/treatment characteristics were assessed using univariate and multivariate logistic regression analysis.
Results: 1676 courses of palliative thoracic RT were delivered to 1584 lung cancer patients. Median survival was 20 weeks. 12% of palliative thoracic RT courses were delivered in the last 4 weeks of life, with short fractionation schedules and simple RT planning techniques used more frequently near EOL. Of RT courses delivered in the last 4 weeks of life 89% were courses of 1 – 5 fractions, 75% were completed as prescribed and 94% involved simple 1 – 2 field RT techniques. Receipt of RT in the last 4 weeks of life was associated with male gender, younger age, poor performance status, metastatic disease, small cell carcinoma histology and no prior chemotherapy.
Conclusion: Further study and standardization of quality indicators for palliative RT utilization near EOL is required. Whilst clarification occurs, physicians should consider the prognosis of patients with incurable lung cancer and the realistic expectation of benefit from palliative thoracic RT when considering treatment indications and fractionation schedules.
The Vancouver Rapid Access (VARA) clinic was designed to provide palliative radiotherapy and holistic care to patients with incurable lung cancer. Analysis of the pilot phase demonstrated improved radiotherapy wait-times and access to supportive services compared to standard practice. This study aims to prospectively assess the impact of the clinic on patient reported symptoms and quality of life. Patient assessments are completed at baseline and by a telephone follow up four-weeks later using Likert scales adapted from the Edmonton Symptom Assessment System (scale 0–10) and European Organization for Research and Treatment of Cancer questionnaires (scale 1–4). Patient reported outcomes at follow-up are compared to baseline using wilcoxon signed-rank test for categorical variables and paired sample t-test for continuous variables. Baseline data was collected on 125 patients, 109 received palliative radiotherapy (87%). At the 4 week follow up, 22 patients had died. Seventy-one of the remaining 103 patients completed the follow-up questionnaire, resulting in a 69% response rate among survivors. The mean patient reported overall health score, improved from 4.8 to 6.1 (p<0.01). All respiratory symptoms except chest pain (p=0.06) were associated with a statistically significant improvement after the clinic, whereas all respiratory symptoms improved post radiotherapy. Mean bone pain scores decreased from 5.5 to 2.7 (p<0.01). Assessment of symptoms secondary to brain metastases is limited by small patient numbers. The VARA clinic provides timely access to palliative radiotherapy and supportive services resulting in improved patient reported outcomes. Despite a high symptom and disease burden, patients report improved overall health and palliation of respiratory symptoms and bony pain. The studies completed on the VARA clinic to date, continue to support its value in our center.