Five-year OS was 57 and 27% for the predicted 'Favourable' and 'Unfavourable' classes, respectively.
In the BSBM system, the difference between the 2 unfavourable classes is not statistically significant.
However, the most unfavourable class contains only 2 patients and the most favourable class only 7. For the score developed by Rades et al., the difference between the 2 unfavourable classes is not statistically significant either.
Applied to these samples, the seven-gene OPM defined a 'Favourable' class (n=187; 51%) and an 'Unfavourable' class (n=179; 49%) that strongly correlated with survival.
Moving from Radiation Therapy Oncology Group (RTOG)'s RPA to their new 4-tiered GPA score, the size of the most unfavourable class can be reduced from 39to34%4%.
Once the best model was defined (OPM), a prediction score, defined by a Cox resulting linear function, was then calculated for each sample, thus defining two classes: the 'Unfavourable' class with a positive score and the 'Favourable' class with a negative score.
Importantly, when applied to a large independent validation set (N=366), which represents so far the largest one reported in the literature, our model maintained its strong and independent prognostic value in multivariate analysis with 5-year OS of 57% in the 'Favourable' class and 27% in the 'Unfavourable' class.
From this 94-gene list, we established a seven-gene OPM able to classify, independently from classical prognostic features, our samples in two classes with different clinical outcome: a 'Favourable' with 5-year OS of 56%, and an 'Unfavourable' class with 5-year OS of 10%.
However, the rate of clinical complete response (CCR) was higher in the 'Favourable' class than in the 'Unfavourable' class (82 vs 46%), suggesting that the prognostic value of the OPM might be partly related to some predictive value for response to chemotherapy.
The 'Favourable' class contained 121 of the 194 alive patients and the 'Unfavourable' class contained 106 of the 172 deceased patients (Se=61.6%, Sp=62.4%, odd ratio=2.7, 95% CI=1.7 4.2; P=6.1E-06, Fisher's exact test), thus confirming the prognostic value of our OPM in a large and independent data set.
The prediction score (OPM) defined two classes: 'Unfavourable' (positive score) and 'Favourable' (negative score).
