Protocol compliance is of paramount importance: for example, Peters et al. demonstrated that major deviations from protocol in radiation therapy trials were associated with poorer overall survival outcomes, underscoring the need for rigorous review processes. Peters et al J Clin Oncol 28(18):2996-3001, 2010. (PubMed)

The ICR involves the prospective or retrospective evaluation of radiotherapy datasets to assess protocol compliance on an individual patient level. Reviews are performed by designated experts, approved by the Study Coordinator for each trial. An appropriate person must perform an ICR; generally, this means that the delineation reviews are performed by radiation oncologists, while dose and plan reviews are conducted by medical physicists.

Trial-specific ICR requirements are defined in the protocol and further detailed in the RTQA guidelines.

Review timing and process

ICRs may include selected patients or all patients and may be performed prospectively or retrospectively. The ICR requirements are defined in the trial protocol.

Prospective review

Prospective review occurs before radiotherapy starts, allowing protocol deviations to be identified and corrected. Feedback is typically provided within 2 business days; any revised plans which address identified corrections to be protocol compliant, must be resubmitted within protocol-defined timelines.

Retrospective review

Retrospective review occurs after radiotherapy has started or been completed. Performing a retrospective review allows us to characterise protocol deviations and whether these could impact the trial endpoint analysis. Feedback is typically issued to the treating institution within 3 months of submission

Review Outcomes

Cases are evaluated with one of four final results:

  • Acceptable: The radiation therapy treatment was delivered to the patient according to the protocol.
  • Acceptable Variation: The radiation therapy treatment was delivered not according to all protocol specifications, but no clinical impact affecting the trial outcome is expected due to the deviation(s). The observed protocol deviations do not exceed the defined protocol criteria for an acceptable variation.
  • Unacceptable Variation: The patient has been planned/treated not according to the protocol, and the deviation(s) could have a clinical impact that would affect the trial outcome. The variation(s) exceed the protocol’s defined criteria for an unacceptable variation. The consequence of the deviation(s) is deemed significant enough by the trial Principal Investigator/RTQA reviewer to increase the trial’s uncertainty and thus may increase the probability that the true trial outcome is obscured if the patient’s data were included in the trial’s final analysis.
  • Justified Unacceptable Variation: The planned/treated volume delineation and/or dose constraints did not meet all the protocol specifications, and the variation(s) exceed the protocol’s defined unacceptable variation criteria. The unacceptable variation radiation therapy treatment is delivered due to clinical necessity as perceived by the treating physician. The consequence of the deviation(s) is significant enough by the study principal investigator to increase the study’s uncertainty and thus might increase the probability that the true study outcome is obscured if the patient’s data were included in the study’s final analyses. The institution is not penalized for this treatment variation.