NorthWest Biotherapeutics Inc (NWBO)

[sd_investor_22]

For all the conversations relating to pseudo vs rapid....again, its pretty clear from the literature that the scientific community has not settled on how to tell the difference between pseudo and rapid, especially in the time frame necessary to enter the patient into a clinical trial. It muddies the water when trying to analyze whether the tx is working.

Here is yet another research paper abstract that shows that there are indicators, potentially, but it concludes that more research is needed. This is from 2012 looking at data from 2005 thru 2009. There are other papers, looking at others techniques, all generally being conducted now and to state that any one group has the magic ability to determine what is going on is false. Over time, yes, but not when early decisions need to be made.

Int J Oncol. 2012 Apr;40(4):923-8. doi: 10.3892/ijo.2011.1260. Epub 2011 Nov 11.
High levels of cellular proliferation predict pseudoprogression in glioblastoma patients.
Pouleau HB1, Sadeghi N, Balériaux D, Mélot C, De Witte O, Lefranc F.
Author information
Abstract
Radiochemotherapy (RT) with concomitant followed by monthly temozolomide (TMZ) chemotherapy is the gold standard for the treatment of glioblastoma (GBM) patients. GBM patients can experience transient radiological deterioration after concurrent RT/TMZ that stabilizes or even resolves after additional cycles of adjuvant TMZ, a phenomenon defined as radiological pseudoprogression. The aim of this retrospective study was to identify a reliable marker associated with pseudoprogression processes. Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2005 and 2009. Predictive factors for pseudoprogression were analyzed from clinical, radiological and biological data. Of the 130 analyzed patients, 63 underwent RT/TMZ treatment followed by cycles of TMZ and were evaluated for radiological responses every two months by magnetic resonance imaging. Early progression was confirmed in 52% (33/63) of the patients, and, within this group, 21% (7/33) displayed evidence of pseudo-progression. The predictive factors were evidenced in terms of clinical or radiological findings. In GBM patients, the level of cellular proliferation (Ki67 indices) emerged as a statistically significant prognostic marker for distinguishing pseudoprogression from actual progression. Our observation, suggesting that GBM associated with a high level of cellular proliferation may differentiate tumor progression from pseudoprogression, warrants further investigation in a large multi-center prospective study.

We can look at subtle wordsmithing in protocols and disclosures and try to infer what was really meant by a particular comment, or you can just look at what researchers are saying.

Also, note the % of rapid vs total and the % of pseudo within the rapids...the numbers don't match the other study that we were talking about, highlighting the difficulty in modelling this type of stuff. This has 53% early progessors, Stupp had 39%, the report referred to previously here was 5%-30%....careful what you assume what is going on.

I suggest that all rapid progessors don't go into the trial because it makes it difficult to figure out whether the tx is working.

Oh, that is how it was designed and that is what they are doing.