Randomized data assessing the longitudinal quality of life (QoL) impact of stereotactic ablative radiation therapy (SABR) in the oligometastatic setting are lacking.
We enrolled patients who had a ...controlled primary malignancy with 1 to 5 metastatic lesions, with good performance status and life expectancy >6 months. We randomized in a 1:2 ratio between standard of care (SOC) treatment (SOC arm) and SOC plus SABR to all metastatic lesions (SABR arm). QoL was measured using the Functional Assessment of Cancer Therapy-General. QoL changes over time and between groups were assessed with linear mixed modeling.
Ninety-nine patients were randomized. Median age was 68 years (range, 43-89), and 60% were male. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Most patients (n = 92) had 1 to 3 metastases. Median follow-up was 26 months. Because of the previously reported inferior survival of the SOC arm, the time for attrition in QoL respondents to <10% of subjects was shorter in the SOC versus SABR arm (30 vs 42 months). In the whole cohort, QoL declined over time after randomization: There were significant declines in total Functional Assessment of Cancer Therapy-General score over time compared with baseline (P < .001) owing to declines in physical and functional subscales (both P < .001), with no declines in social and emotional subscales. However, the magnitudes of decline were small, and clinically meaningful changes were not seen at most time points. Comparison between arms showed no differences in QoL between the SABR and SOC arms in total score (P = .42) or in the physical (P = .98), functional (P = .59), emotional (P = .82), or social (P = .17) subscales.
For patients with oligometastases, average QoL declines slowly over time regardless of treatment approach, although the changes are small in magnitude. The use of SABR, compared with SOC, was not associated with a QoL detriment.
Radiotherapy-related fibrosis remains one of the most challenging treatment related side effects encountered by patients with head and neck cancer. Several established and ongoing novel therapies ...have been studied with paucity of data in how to best treat these patients. This review aims to provide researchers and health care providers with a comprehensive review on the presentation, etiology, and therapeutic options for this serious condition.
Abstract Purpose To report outcomes of a single institution study of stereotactic body radiotherapy (SBRT) for unresectable cholangiocarcinoma. The dose–volume dependency of the observed ...gastrointestinal toxicity is explored. Methods and materials Twenty-seven patients with unresectable cholangiocarcinoma ( n = 26 Klatskin tumours and one intrahepatic cholangiocarcinoma (IHCC)) were treated by linac-based SBRT. The dose schedule was 45 Gy in three fractions prescribed to the isocenter. Results The median progression-free survival and overall survival were 6.7 and 10.6 months, respectively. With a median follow-up of 5.4 years, 6 patients had severe duodenal/pyloric ulceration and 3 patients developed duodenal stenosis. Duodenal radiation exposure was higher in patients developing moderate to high-grade gastrointestinal toxicity with the difference in mean maximum dose to 1 cm3 of duodenum reaching statistical significance. A statistically significant association between grade ⩾ 2 ulceration and volume of duodenum exposed to selected dose levels was not established. Conclusion The outcomes of SBRT for unresectable cholangiocarcinoma appear comparable to conventionally fractionated chemoradiotherapy with or without brachytherapy boost. The practical advantages of SBRT are of particular interest for such poor prognosis patients. Patient selection, however, is key in order to avoid compromising such practical gains with excessive gastrointestinal toxicity.
Lung cancer is the second most diagnosed cancer and the leading cause of cancer-related mortality in Canada. Surgical resection is the treatment of choice for patients with stage I non–small-cell ...lung cancer (NSCLC). However, 20% to 30% of them are deemed medically inoperable and may be offered radiation therapy. Standard external-beam radiation therapy (EBRT) is associated with high rates of local recurrence and poor long-term survival. Stereotactic ablative radiation therapy (SABR) is increasingly being proposed for inoperable patients, and the use of this treatment modality for operable patients is also being contemplated. The objective of this guideline is to review the efficacy and safety of SABR in these two clinical situations and to develop evidence-based recommendations.
A review of the scientific literature published up to December 2013 was performed. A total of 44 publications were included.
Considering the evidence available to date, the Comité de l’évolution des pratiques en oncologie recommends the following: (1) for medically operable patients with stage T1-2N0M0 NSCLC, surgery remains the standard treatment because comparative data regarding the efficacy of SABR and surgery are currently insufficient for SABR to be considered an equivalent alternative to surgery for these patients; (2) for medically inoperable patients with stage T1-2N0M0 NSCLC or medically operable patients who refuse surgery, SABR should be preferred to standard EBRT (grade B recommendation); (3) the biological equivalent dose (BED10) used for SABR treatment should be at least 100 Gy (grade B recommendation); (4) for patients with a central tumor, a large-volume tumor (large planning target volume) or severe pulmonary comorbidity, a risk-adapted schedule should be used (dose reduction or increase in the number of fractions; grade B recommendation); (5) the choice of using SABR to treat NSCLC should be discussed within tumor boards; treatment with SABR (or with standard EBRT) should not be considered for patients whose life expectancy is very limited because of comorbidities (grade D recommendation).
Abstract Purpose To determine the prognostic role of co-morbidity in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Methods ...and materials Between 2000 and 2007, 88 consecutive early-stage medically inoperable NSCLC patients were treated by linac-based SBRT. The dose was either 45 Gy or 67.5 Gy in three fractions prescribed to the isocenter. Baseline co-morbidities were retrospectively retrieved by consultation of a formal electronic registry of diagnoses as well as patients’ charts. The age-adjusted Charlson Co-morbidity Index (CCI) was scored for each patient and subjected to univariate and multivariate analysis. Results With a median follow-up of 44 months, the actuarial local control rate at 4 years was 89% while the median overall survival was 22 months. The median age-adjusted CCI score was 5. The age-adjusted CCI was a significant predictor of overall survival on both univariate ( p = 0.002) and multivariate analysis ( p = 0.011). Patients with an age-adjusted CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more. Conclusion The number and seriousness of co-morbidities predict overall survival in medically inoperable early-stage NSCLC treated with SBRT. Because the determination of medical operability is frequently based on both objective measures and subjective clinical judgment, it is recommended that co-morbidity be formally indexed in all studies examining the outcomes of SBRT.
Abstract Background Standard treatment for unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed ...by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and non-protocol patients. Methods and materials Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013. Patients received 2 cycles of carboplatin AUC=5 IV on day 1 and gemcitabine 1000mg/m2 IV on days 1 and 8 every 3 weeks, followed on day 50 by CRT, 60Gy/30 over 6 weeks, concomitantly with 2 cycles of paclitaxel 50mg/m2 IV and gemcitabine 100mg/m2 IV on days 1 and 8 every three weeks. Results The median overall survival was 23.2 months. With a median follow-up of 23.8 months, the 3, 4 and 5 year overall survival was 38%, 30%, and 26% respectively. The median and 5-year progression-free survival rates were 12.5 months and 25% respectively. Rates of grade ≥ 3 hematological, esophageal and respiratory toxicity were 20%, 10% and 10% respectively. Forty-eight patients received further lines of chemotherapy. Conclusion The present analysis affirms the favorable toxicity profile of this novel induction chemotherapy, without apparent compromise in clinical outcomes when compared to regimens using immediate concurrent CRT.
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.
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 α 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.
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.
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.
Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
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