J Natl Cancer Inst 2014 Aug
Phase II study of accelerated hypofractionated three-dimensional conformal radiotherapy for stage T1-3 N0 M0 non-small cell lung cancer: NCIC CTG BR.25.
Abstract
Background
A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available.
Methods
Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour volume (GTV) was the primary tumor only, and the planning target volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary tumor control rate. Toxicities were measured using the Common Terminology Criteria for Adverse Events version 3.0.
Results
The median follow-up of patients was 49 months (range = 21-63 months). The median age of patients was 75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence interval [CI] = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI = 57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI = 13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30 to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%)
Conclusions
Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.
Related Questions
How would you approach a mediastinal-only presentation of squamous cell carcinoma of the lung s/p lymph node biopsy consistent with lung origin, with PET positive for only mediastinal disease?
First, I would confirm no prior cancer diagnosis, review in detail with a multidisciplinary tumor board, and try to rule out the non-lung primary site. If no primary can be found, and PET demonstrates limited disease only in the mediastinum/hilum, then I would just treat the disease that you can see...
Do you ever consider small vessel doses when determining your dose for SBRT?
We do not constraint dose to the azygous vein, or other small vessels when giving SBRT. We similarly do not constrain dose to large vessels such as the IVC or the Aorta either, and I am un-aware of specific reports of toxicity to these structures. Structures that I am particularly concerned about ar...
How do you treat inoperable T1-2N0 apical lung cancers near the brachial plexus but without extension outside the lung?
This is a challenging question, and there are certainly a range of reasonable answers. I would agree with @Dr. First Last that the Forquer/Timmerman paper establishes there is significant risk of plexopathy when exceeding 24-26 Gy in 3 fractions. On the other hand SBRT offers superior local control ...
What is your preferred dose and fractionation schedule for a patient with a stage III non-small cell lung cancer, whose comorbidities preclude chemotherapy, but has good enough performance status to warrant an attempt at longer-term local control?
This is a very good question. I'd say the answer to this one is evolving! Typically the patients who cannot tolerate either sequential or concurrent chemotherapy for locally-advanced NSCLC are quite frail and/or have comorbidities that are significant. The results using radiation alone for Stage III...
Would you use SBRT to treat a >5cm NSCLC with chest wall invasion in a medically inoperable patient?
This is a very relevant and interesting question as the patterns of practice and indications for lung SBRT continue to evolve. It also fits in nicely with two recent retrospective reviews we conducted at the Cleveland Clinic using our 10-year old lung SBRT data registry. Addressing the first compone...