iRECIST recommends that imaging be repeated 4-8 weeks after iUPD was detected. Questions: Scans were repeated 9 weeks after the iUPD was first detected, because of scheduling issues. Can those scans not be used? Answer: In order to ensure that patients do not have real and continuing disease progression that requires a change in management,
Group: Questions and clarifications
Can imaging be used to confirm progression, even when done LESS than four weeks after the scans that showed iUPD
Scenario: patient was confirmed to have no brain lesions at baseline. iUPD is assigned at timepoint 3 due to new liver lesions. 14 days later the patient has an unscheduled CT scan for new symptoms which shows a new lesion in new site. 4.5 weeks after the iUPD was first documented repeat imaging shows a
In the Lancet publication, in the section on Timepoint and best overall response it is stated that “The protocol should establish how missing response assessments will be handled. Assessments that are not done or are not evaluable should be disregarded. For example, an iUPD followed by an assessment that was not done or not evaluable,
In RECIST 1.1 the usual principle used is that once a PR has been assigned, and confirmed (if required), then the best response is always PR even is subsequent TP measurements no longer quite meet the criteria (providing that the criteria for PD are not met). The same principles hold for iRECIST as shown below.
RECIST 1.1 principles should be followed. In general, when a lesion cannot be assessed the entire timepoint assessment should be considered to be not evaluable (NE). RECIST 1.1 describes how to manage lesions that have become so small they cannot be measured. iRECIST adds an additional element, as progression is only confirmed at the “next
iDOR is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of PD (iUPD confirmed as iCPD. iDOR is only defined for subjects who have best overall response of iCR or iPR. If a patient has iPR (#1) followed by a iUPD (#1) which is not
New lesions by themselves may define iUPD (when they appear), or iCPD when they increase in size (5mm or more if they are target, or any increase if non target), or another lesion appears. However, as noted, the rules of RECIST1.1 always apply – if new lesions appear but then decrease in size or stay
Per RECIST 1.1, in exceptional circumstances, unequivocal progression in non-target disease may result in RECIST 1.1 PD / iRECIST iUPD. Any increase in non-target tumour burden at the next assessment would allow iCPD to be confirmed; the increase does NOT have to be unequivocal (per RECIST 1.1) again. The same is true for new lesions.
Classification of assessments (Time Point Responses (TPR)) after unconfirmed progression (iUPD) has occurred but was not subsequently confirmed (iCPD), specifically when iPR (partial response) can be assigned.
In the paper and as reproduced below, scenario B shows that the appearance of a new lesion (NL) does not preclude the next assessment (time-point, TP) being iPR (immune partial response, because of further shrinkage of target lesions after the new lesion is recorded), while in scenario D, iUPD (i-unconfirmed progressive disease) occurs at TP3