Yeah, because the regular Ihub posts certainly are not! 😂
The absolutely worthless twitter reposts are getting out of hand.
And then ex and the usual ORR endpoints garbage:
It seems as if you haven't got the elementary knowledge of RECIST and IRECIST, so let's start there.
RECIST (Response Evaluation Criteria in Solid Tumors) is a standardized set of criteria for measuring tumor response to cancer treatment, while iRECIST is a modified version of RECIST specifically designed for cancer immunotherapy trials to account for unique response patterns, such as pseudoprogression. iRECIST allows for tumor burden to initially increase before subsequent shrinkage, preventing the premature discontinuation of treatment that may be beneficial.
What is RECIST?
Think of RECIST as the ruler doctors use to measure cancer on scans.
If tumors shrink a lot (30% or more), that’s counted as a “response.”
If tumors grow a lot (20% or more, or new ones appear), that’s “progression.”
If the change is in-between, it’s called “stable.”
This is simple and works well for chemo or targeted drugs, where tumors usually shrink quickly if the drug works.
Why RECIST doesn’t always work for immunotherapy
Immunotherapy is different. When the immune system floods into a tumor, it can make the tumor look bigger on scans before it gets better. Sometimes new tiny spots show up as the immune system wakes up.
This is called pseudoprogression - it looks like the cancer is worse, but really it’s the immune system doing its job.
If we stick to the old RECIST ruler, these patients would be marked as “treatment failed” and taken off therapy - even when the treatment was working.
What is iRECIST?
iRECIST is the updated measuring tape made just for immunotherapy.
The first time a scan shows “progression,” doctors don’t immediately call it failure. Instead, it’s marked as “unconfirmed progression.”
The patient stays on treatment (if they’re otherwise stable) and comes back in about a month for another scan.
If the tumor really keeps growing, then it’s confirmed progression. If it shrinks or stabilizes, it’s reclassified as a response or stable disease.
When to use which
RECIST: Use for old-school chemo or targeted drugs - they kill cells directly and tumors usually shrink right away.
iRECIST: Use for Checkpoint inhibitors, cell therapies, cancer vaccines, and other immuno-oncology regimens where pseudoprogression and delayed responses are plausible. Plan a confirm scan at 4–8 weeks after any first sign of progression.
Bottom line
RECIST is a quick yes/no ruler: smaller = good, bigger = bad.
iRECIST adds a second check: don’t throw away a working immunotherapy too soon, give it time to show if the swelling is real cancer growth or just the immune system at work.
Now we have updated you with the elementary, let's continue:
What “ORR” actually means (so the math is honest)
ORR = CR + PR. That’s the share of patients with complete response or partial response. National Cancer Institute: “the percentage… who have a partial response or complete response.”
PR threshold under RECIST 1.1 = ≥30% shrinkage in the sum of target-lesion diameters. Best overall response (BOR) is taken across the whole on-treatment period, with confirmation rules.
What DCVax-Direct Phase 1 was designed to do
Design (official record): “The study comprises a Phase I component during which the optimal dose… will be identified, followed by a Phase II component to determine if… DCVax-Direct… has the ability to reduce tumor growth.” (NCT01882946).
Phase 2 efficacy yardstick (company launch): “The trial will then proceed directly into the Phase II stage to test the efficacy… The primary endpoint for measurement of efficacy will be tumor regression (i.e., shrinkage or elimination).”
What the peer-reviewed Phase 1 paper actually reports
Key clinical signal (verbatim from abstract): “Stable disease (SD; best response) at week 8 was associated with increased overall survival.” Intratumoral aDC injections were “feasible and safe.”
The full text quantifies the survival link with the familiar statistic (p = 0.047) and discusses cytokine correlates.
What Table 3 is for: a correlative table pairing each patient’s week-8 status (SD or PD) with cytokine/phenotype data, used to show that stronger DC function linked to better outcomes. The abstract itself highlights the SD -> OS association; there is no trial-level ORR in that paper.
Why week-8 math DOES NOT EQUAL ORR: ORR requires CR/PR under RECIST thresholds and the best overall response across time. A single week-8 snap
Pseudoprogression is real and accounted for by iRECIST. iRECIST (RECIST Working Group, Lancet Oncology): “iRECIST requires the confirmation of progression in order to rule out - or confirm - pseudoprogression.”
Direct tumor-kill evidence in this program (biopsies during the trial): “biopsies… in 3 of these 9 patients now show no live tumor cells in the tumor that was injected,” even though scans showed enlargement - the classic immune-cell infiltration effect.
Program status (why “stopped after a negative P1” doesn’t match the filings)
Company filings describe Phase 1 completion and an intent to proceed to Phase 2 as resources permit: “A 40-patient Phase I trial has been completed… We plan to work on preparations for Phase II trials of DCVax-Direct as resources permit.”
Earlier filings used the same “proceed as resources permit” language, consistent with prioritizing DCVax-L spend.
SUM UP OF FALLACIES
The core misunderstandings
1) Mixing up phase objectives
Phase 1 asks:“Is it safe? What dose? Any biological signal?”
Phase 2 asks: “Does it shrink tumors by RECIST rules (ORR)?”
Treating Phase 1 as an ORR gate confuses feasibility with efficacy. When someone demands a Phase-2 endpoint from a Phase-1 report, the argument is incoherent by design.
2) Misdefining ORR
ORR = CR + PR under RECIST 1.1 thresholds, with PR ≥30% shrinkage and best overall response across the treatment period. Calling a week-8 status table an “ORR readout” ignores the “best-overall-response over time” rule and the confirmation logic that underpins RECIST.
3) Treating Table 3 like an ORR table
Table 3 (in the CCR 2018 paper) is correlative: week-8 SD/PD + cytokine/phenotype per patient to show biology–outcome links. Using that table to “compute ORR” is a category error - like reading a lab values sheet and calling it a radiology report.
4) Ignoring pseudoprogression and iRECIST
Immunotherapies can cause early swelling or small new foci that later regress once immune cells flood the tumor. iRECIST exists to confirm progression before labeling failure. Declaring “failure” from the first flare erases the very reason iRECIST was created.
The fallacies driving the claims
Straw man: “Phase 1 had to show ORR to proceed.” The record sets ORR for Phase 2, while Phase 1 focuses on safety/feasibility and biology.
Cherry-pick / snapshot math: Lifts a single week-8 SD/PD snapshot and declares it “0% ORR,” ignoring best overall response across time.
Category error: Uses a biomarker table to claim an imaging endpoint.
Argument from silence: “The paper didn’t publish ORR, therefore ORR = 0.” Absence of an efficacy metric in a Phase-1 report never equals zero; it equals “not the endpoint in this phase.”
Moving goalposts: When survival linkage to SD is shown, the critique shifts back to “no shrinkage,” skipping iRECIST and pseudoprogression entirely.
How to sanity-check any ORR claim (a five-step quick test)
Which phase? If Phase 1, expect safety + biology; if Phase 2, expect ORR.
What endpoint? Is the claim about ORR or DCR or landmark SD? Use the right definition.
What time frame? ORR uses best overall response, not a single early visit.
Which criteria? If immunotherapy, check iRECIST and the confirmation rule.
What did the paper say verbatim? Read the abstract and results lines before accepting second-hand summaries.
Yes ex ... you are free to fud further. See ya soon!
AI
