Radical radiotherapy is indicated for patients with stage I—II NSCLC who are unfit for surgery, or have good performance status and stage III disease which can be encompassed in a radical volume.
Patients with inoperable non-small cell lung cancer (NSCLC) have a 20-30% chance of surviving two years if fit for radical radiotherapy and a similar chance of surviving one year if not. No randomized trial has examined the role of radical radiotherapy in these outcomes.
The standard international dose is 60 Gy in 30 fractions over 6 weeks. Attempts to increase dose by hyperfractionation without acceleration have not shown any benefit. CHART, delivering 54 Gy in 36 fractions over 12 days has afforded a 9% survival advantage at two years compared with standard therapy. No trial has compared these regimes with shorter 3-4 week schedules (e.g. 50-55 Gy in 20 fractions), which remain popular in the UK.
CHART is logistically difficult to deliver because of weekend treatment; its modification to exclude weekends, CHARTWEL, delivers 60 Gy in 40 fractions over 17 days. Modification has not yet been compared to other schedules.
No randomized trials have examined what volume should be irradiated. The standard in most of the world is the primary tumour and hilar and mediastinal lymph nodes, with a 1-2 cm margin. Retrospective comparisons have not demonstrated any advantage over volumes encompassing tumour and involved lymph nodes only. In dose escalation studies with conformal therapy, adjuvant nodal irradiation constrains the radiation dose delivered to the primary tumour. Omitting uninvolved nodal groups does not appear to increase local relapse rate.
The Non-Small Cell Lung Cancer Collaborative Group (1995)1 overview suggested a 2% increase in 5-year survival when cisplatin-based chemotherapy is added to radical radiotherapy. The RTOG 88-08 study reinforces these conclusions, with a 4-year survival advantage of 5% with combined therapy.
Chemotherapy delivered synchronously with radiotherapy has not yet been shown to increase survival in randomized trials and certainly adds to toxicity. A recent review of the RTOG database reported a significant increase in morbidity in combined regimes. Over one-third of patients receiving chemotherapy and hyperfractionated radiotherapy experienced severe oesophagitis.
Even with CHART, long-term local control is poor. Dose escalation with conformal therapy is being explored to improve this. Using normal tissue complication probabilities to estimate a 'safe' dose of radiotherapy, up to 92.4 Gy has been delivered to small volumes without significant morbidity.
A meta-analysis of randomized trials of post-operative radiotherapy for completely resected NSCLC has shown impaired survival following irradiation in patients with NO and N1 disease. There is evidence that radiotherapy affords an improvement in local control for patients with N2 disease. The best results have been reported in an American trial delivering 50 Gy in 25 daily fractions.
For many patients with advanced NSCLC, radiation therapy is a key component in symptomatic treatment. Palliative radiotherapy is effective for:
Radiotherapy can also ameliorate systemic symptoms such as anorexia and weight loss.
MRC trials have shown equivalent survival and symptom control for 1-, 2-, and 10-fraction regimes, establishing the shorter courses as the treatment of choice for symptom control in advanced NSCLC. However, these short schedules are associated with pain and flu-like symptoms in up to 40% of patients. A transient reduction in peak expiratory flow rates may occur. Most patients receiving two fractions suffer moderate to severe oesophagitis.
A third MRC trial suggested that higher-dose palliative therapy (39 Gy in 13 daily fractions) did offer modest survival advantage for good performance status patients with large tumours; comparable to that seen with cisplatin-based combination chemotherapy.
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