No, that is not what we were arguing about. Instead we were mostly arguing whether any patients who exhibit Apparent Early Tumor Progression (AETP) on Month 2 scan would (you) or would not be (me) removed as a progression free survival event. (Brad's scan is another subject entirely; you saw a measurable BASELINE scan that grew 2 weeks after initiating therapy; and I saw a non-measurable baseline scan that required retrospective monitoring of possible 2 weeks post treatment enhancement induced scan changes.)
As for this Phase III Month 2 scan, you felt that MacDonald considered AETP patients (>25% of enhancing disease) that showed up after chemoradiation as an automatic PFS event. Whereas, I perceive that MacDonald is now RANO and retrospectively reviews all the POST BASELINE scan (Month 2 in this Phase III) by use of follow-up scan to separate true TUMOR progression from Pseudoprogression.
The first three months after concurrent chemoradiation are known to include Pseudoprogression events that mimic progression. That phenomenon showing up in the main arm after concurrent RT/TMZ may have been reduced due to the exclusion criteria (removal of evidence of disease patients). However, I doubt Pseudoprogression RT/TMZ induced early scans of new "mimic progression" appearances will have completely gone away. Given the fact that the trial was randomized by MGMT status, I see both arms as having been at equal percentage risk of early scans after concurrent RT/TMZ mimicking that phenomenon. But it doesn't matter as I still see that a follow-up period is necessary and it is done in standard practice to confirm true progression.
As you are well aware the RANO criteria, which became standard as of 2010, does not call disease progression mimicking patients official "progression" during the first 12 weeks after chemoradiation therapy as it needs to account for Pseudoprogression first. You think that somehow this trial will not be abiding that RANO rule. You think this trial will have no choice but to blindly call all Apparent Early Tumor Progression (AETP) --that may end up being psPD -- as progression free survival event. You perceive that as MacDonald. Whereas, I think early scans are retrospectively reviewed in order to confirm a progression threshold has been crossed, and that is a standard practice now, regardless of criteria. Pseudoprogression is known to occur in the standard of care patients during the first 12 weeks after chemoradiotherapy and I see concurrent RT/TMZ being a possible culprit of AETP scans, I think it is IMPOSSIBLE to call scans within the field of radiation "progression" without a retrospective review.
I also think because that in clinically practice that RANO rule for looking out for RT/TMZ responding patients (in order to avoid prematurely stopping or altering effective therapy) and that Psuedoprogression rule can not be bypassed. Since STUPP protocol became standard it quickly became apparent that true early TMZ failure can only be determined with serial scans. There is no imaging biomarker that "automatically" confirms GBM progression for newly diagnosed concurrent RT/TMZ patients. And since TMZ was brought upfront with radiation the incidence of Pseudoprogression was addressed by that RANO clause. Patients who have not progressed can be determined by follow-up. As such I feel that no IRB will approve a "automatic" fail image biomarker be used in this Phase III trial, particularly as one does not exist an image biomarker for GBM progression.
I also believe that the IRB will not allow any AETP scan to be automatically determined as treatment failure in that < 12 week post concurrent RT/TMZ period. Adjuvant TMZ was also being given in that immediate Post RT period. It will be impossible to know if main arm patients Month 2 scans are TMZ treatment related Pseudoprogression effects. And considering that TMZ follow-up imaging is standard now to look out for early Psuedoprogression, I see it as impossible to rule any scan automatic progression in that <12 week window. I see this approach being used on Month 2 scans:
Response Assessment
Central review of pre- and postcontrast T1-weighted and FLAIR images was performed by an independent radiologist who was blinded to clinical data and who obtained standard bidimen- sional measurements on T1-weighted postcontrast images. The reader was also blinded to the order of the imaging time points to avoid bias in tumor measurements from expected treatment effects. Clinical evaluations were performed by the treating oncologists. Tumor response was determined according to the updated Response Assessment in Neuro-Oncology (RANO) criteria for malignant gliomas [2], taking into account clinical performance, dose of steroids, dimensions of contrast- enhancing lesions, and extension of tumor-related FLAIR signal abnormalities. Patients who demonstrated signs of progression on imaging inside the radiation field during the first 12 weeks after completion of radiation were considered to have apparent early tumor progression (AETP) and (if clinically feasible) were maintained on the same treatment regimen and imaging surveillance. During follow-up, patients with lesions that maintained growth despite treatment were considered to have TTP. PsP was diagnosed in patients with stable or regressing lesions for a period of at least 6 months without changes in therapy (Fig. 1). Repeat biopsies or resections at the time of AETP were not deemed necessary by the treating neuro-oncologists for pathologic analysis in most cases, given the increasing recognition of PsP [5, 21–23].
Market Data 
Markets 
AI
