Replies to post #54205 on NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

This even more than the last link proves the point. A significant number of these patients continued to show worsening scans past 3 months even though they ended up being psPD. They were labeled ePD under RANO crit:

Abstract
BACKGROUND: Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe).

METHODS: Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed.

RESULTS: Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001).

CONCLUSIONS: Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.

So if almost 30% of those thought to be ePD in the info arm ended up psPD, how would that affect the data? Note that even more of the above would have been thought ePD if the cut off was 2 months instead of 3 months (let alone 10 weeks)

[Doc logic]

Pyrrhonian,

From a layman's perspective this reasoning would appear to be correct but doesn't this essentially cast doubt on the 3 expert radiologist panel that adjudicate these images? Haven't the images become more reliably interpreted by advances with image guidance and staining. Perhaps the 12 weeks needed in the past has been improved upon so that these experts are willing to attach their names to the readouts. I don't think they want to be known as quacks. I certainly would not jeopardize a well paid career for a single study for a no name biotech. Best wishes.