Efficacy
The evidence supporting this protocol is provided by a 2015 Cochrane review by Stevens et al. of 14 randomised trials including 3576 patients.r All trials confirmed improvement of thoracic symptoms following a variety of RT regimens, and relatively mild toxicity with shorter RT schedules. There is no strong evidence that any regimen gives better palliation. When stratified by performance status, the meta-analysis showed no significant difference in 1-year overall survival between regimens. However, only 56% of patients could be stratified thus casting doubt on the conclusions made in this analysis. This conclusion contradicts the results of previous systematic reviews which suggest that there may be a benefit to giving a higher dose to patients with better performance status.rr
NCCN continues to endorse higher doses in patients with good performance status on the basis of a previous meta-analysis by Fairchild et al. 2008.r This needs to be balanced against greater incidence of toxicity as well as patient inconvenience.
IMRT may be considered to reduce the dose to organs at risk. A planning study by Granton et al. have suggested that oesophageal sparing IMRT can significantly reduce the rate of oesophagitis without compromising local control.r
Concurrent chemotherapy
Two randomised control trials, Nawrocki et al. and Strom et al. have demonstrated a survival benefit with the use of concurrent chemoradiation therapy compared to radiation therapy or chemotherapy alone in patients with stage III NSCLC.rr Whilst these trials have used moderate hypofractionation 30Gy in 10 fractions and 42Gy in 15 fractions, the optimum radiation therapy dose and chemotherapy remains to be defined.
In the Nawrocki trial, only a minority of patients (13/48) from the radiation alone arm received chemotherapy on progression, due to poor performance status. Therefore, the use of concurrent chemoradiation as used in these trials has not been compared to sequential treatment.
On the basis of these trials, the updated 2018 ASTRO guidelines recommend concurrent platinum-doublet chemotherapy administration for those that meet the following criteria:r
- Stage III NSCLC
- Not eligible for curative-intent therapy
- Suitable for chemotherapy
- ECOG 0-2
- Life expectancy > 3 months
Figure 1. Cochrane analysis of one-year overall survival for "more fractionated" vs "less fractionated" regimes.
The Cochrane Collaboration 2015r