Review Question
What is the best way to give radiotherapy to patients with incurable lung cancer. What doses give the best balance between symptom control and side effects? Does giving more radiotherapy improve the chance of a patient being alive in one or two years?
Background
In most developed countries lung cancer is one of the commonest tumours. Only 10 to 20% of patients can have surgery with a chance of cure. For many of the rest radiotherapy to the chest is used to relieve symptoms of cough, breathlessness and pain. The number of radiotherapy treatments given and the dose of each treatment varies widely around the world. Since the late 1980s, many trials have tried to answer which is the best radiotherapy schedule to relieve symptoms without causing too many side-effects.
Study Characteristics
Fourteen trials, including 3576 patients, were found that compared at least two different radiotherapy regimens. All involved patients with incurable lung cancer but the extent of the cancer and the fitness of the patients varied between the studies making direct comparisons difficult.The radiotherapy regimens in the trials varied from a single treatment to thirty treatments over six weeks.This update found no new trials and a meta-analysis (pooling the results of all trials) was carried out to see whether giving higher doses of radiation resulted in longer survival.
All trials reported how long patients lived after their treatment and looked at the effect on symptoms as well as recording side-effects. However, the trials did not use the same methods for recording symptoms and side effects with some using the doctor's assessment and some using the patient's, making direct comparison difficult.
Key Results
This review shows that for most patients, a short course of radiotherapy with only one or two visits, improves common symptoms as effectively as longer courses, without more side effects. There is no strong evidence to support the view that a longer course of radiotherapy may give a better chance of living for one or two years, but it does result in more immediate side effects, especially sore swallowing.
Quality of the Evidence
All the trials were randomised meaning patients involved in the study had an equal chance of getting either treatment. The use of a doctor's assessment of the patient's symptoms in some studies may have led to an under-estimation of the symptoms.
Radiotherapy for patients with incurable non-small cell lung cancer can improve thoracic symptoms. Care should be taken with the dose to the spinal cord to reduce the risk of radiation myelopathy. The higher dose, more fractionated palliative radiotherapy regimens do not provide better or more durable palliation and their use to prolong survival is not supported by strong evidence. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative radiotherapy. In the future, large trials comparing different RT regimens may be difficult to set up because of the increasing use of systemic chemotherapy. Trials looking at how best to integrate these two modalities, particularly in good PS patients, need to be carried out.
Palliative radiotherapy to the chest is often used in patients with lung cancer, but radiotherapy regimens are more often based on tradition than research results. This is an update of a Cochrane review first published in 2001 and previously updated in 2006.
The two objectives of this review were:
1. To assess the effects of different palliative radiotherapy regimens on improving thoracic symptoms in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent.
2. To assess the effects of radiotherapy dose on overall survival in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent.
The electronic databases MEDLINE (1966 - Jan 2014), EMBASE and the Cochrane Central Register of Controlled Trials, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished.
Two authors (FM and RS) independently identified all studies that may be suitable for inclusion in the review.
We updated the search up to January 2014.
Randomised controlled clinical trials comparing different regimens of palliative thoracic radiotherapy in patients with non-small cell lung cancer.
The reviewers assessed search results independently and possible studies were highlighted and the full text obtained. Data were extracted and attempts were made to contact the original authors for missing information.
The primary outcome measure was improvement in major thoracic symptoms (degree and duration). Secondary outcome measures were short and long term toxicities, effect on quality of life and overall survival.
Patient reported outcomes were reported descriptively. Quantitative data such as survival and toxicity were analysed as dichotomous variables and reported using relative risks (RR).
For this update of the review a meta-analysis of the survival data was carried out.
Fourteen randomised controlled trials (3576 patients) were included, with no new studies added in this update.
There were important differences in the doses of radiotherapy investigated, the patient characteristics including disease stage and performance status and the outcome measures.The doses of RT investigated ranged from 10 Gy in 1 fraction (10Gy/1F) to 60 Gy/30F over six weeks, with a total of 19 different dose/ fractionation regimens.
Potential biases were identified in some studies. Methods of randomisation, assessment of symptoms and statistical methods used were unclear in some papers. Withdrawal and drop-outs were accounted for in all but one study.
All 13 studies that investigated symptoms reported that major thoracic symptoms improved following RT.There is no strong evidence that any regimen gives greater palliation. Higher dose regimens may give more acute toxicity and some regimens are associated with an increased risk of radiation myelitis. Variation in reporting of toxicities, in particular the absence of clear grading, means results of the meta-analysis should be treated with caution.
Meta-analysis of overall survival broken down by performance status, a key variable, is included in this update. Further information was sought from all the original authors if stratified data was not included in the original publication. Three published studies contained sufficient data and seven authors were able to provide further information which represented 1992 patients (56% of all patients). The absence of data for nearly half of the patients has affected the quality of evidence.
The meta-analysis showed no significant difference in 1-year overall survival between regimens with fewer radiotherapy fractions compared with regimens with more when patients were stratified by performance status. The results of the meta-analysis of 1-year overall survival for patients with good performance status (WHO performance status 0-1) showed moderately high heterogeneity and a summary result was not thought meaningful. The results of 1-year overall survival for patients with poor performance status was RR 0.96 (95% CI 0.91 to 1.02; moderate quality of evidence).