flipper44,
The counter balance to this discussion about PFS for SOC with "intent for gross total resection" is that greater tumor burden in those in the treatment arm is correlated to reduced benefit from treatment. This conclusion is based on the suggested lower tumor burden threshold limit Dr. Linda Liau mentioned with regard to normalized immune system monitoring capabilities.
Since this trial is seeking the middle group of total patient population responders we know that the percentage of mesenchymal and proneural patients represented will be at reduced levels due to their typical relationship to the outliers in PFS as well as OS. This will still leave a good percentage of mesenchymal and perhaps a subgroup of proneural along with the other subtypes well represented which, upon crossover, would be expected to be at a higher percentage of mesenchymal phenotype than the unrestricted general population. This would probably result in better overall outcomes for all patients in this trial with regard to OS which is what Dr. Linda Liau implied was indeed happening. The question then remains as to whether or not this middle group can still respond better than the typical patient population with regard to PFS. I believe the answer is yes because the trial attempts to skew towards gross total resection. This will favor SOC to some limited extent but should show the stronger correlation towards the treatment arm as the average patient is skewed toward the point that Dr. Linda Liau believes is critical for DC treatment alone. The log benefit curve comes into play twice as much in the treatment arm as you approach the critical tumor cell count point.
A separate point that came to mind today was that Fraunhofer and NWBO agreed to lower patient standards with regard to cell count probably because they wanted to close the manufacturing system more and incorporate TFF or TFF+ improved cell selection techniques developed by Fraunfofer. Since this was being built in late to the trial, all regulators had to be brought on board and the screening hold had to allow for recovery of patient base if some were not accepted after having been enrolled. Did NWBO take a calculated risk along with the Germans? Maybe. What could be the possible benefit? Well maybe speeding up the trial was what they envisioned. With lower total lymphocyte count patients included, PFS events would probably speed up. On the other hand, TFF and potentially improved cell selection could have optimized the product for those who are treated. These patients might have a slower initial response but an optimized secondary buildup. The reason for this is there are fewer cells to recruit as Tregs. The separation between treated and SOC could, therefore, potentially widen which going from October to November for primary completion could be taking into account. Best wishes.
AI
Market Data 
Markets 
