129 Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI 7 results for image-based prediction methods (regardless of whether visual morphologic and/or quantitative) are highly variable with AUCs in many reports not exceeding 0.80; performance levels that will likely not be considered sufficient to impact treatment planning. Response to anti-cancer treatment is a multifactorial process that is not only dependent on tumor size and morphology, but also on other patient-factors and aspects of tumor biology that we cannot hope to capture by imaging. Important next steps in research will therefore be to combine image-based prediction methods with other clinical, histopathological, immunohistochemical and genetic biomarkers that have shown promise as predictors of response and that were unfortunately not available for analysis in this current retrospective study cohort[27,29-33]. Only this way can we hope to achieve a strong enough predictive performance to serve as a basis for clinical decision-making, aiming to further boost personalized therapy in rectal cancer. There are some limitations to our study design, in addition to its retrospective nature. To ensure that it would be feasible for a multitude of readers to complete the full set of study cases within an acceptable timeframe, the cohort size was deliberately kept relatively small. We fully acknowledge that the semi-random selection of patients from a larger cohort (ensuring a balanced sample in terms of representation of data from the different participating centers and response outcomes), may be prone to bias though we are confident that our cohort including data from ten different centers offers a representative sample reflective of everyday clinical routine. The study dataset dates back to 2010, which entails that some MRIs were acquired with ‘outdated’ study protocols. Though we acknowledge these variations may have had an impact on overall scan quality, we believe that these effects will likely be limited considering that evaluations were mainly based on routine T2-weighted imaging which will probably show less variation in quality over time than for example DWI. While the 17 less-expert readers in our cohort were intended to offer a representative sample of radiologists reading rectal MRI in everyday clinical practice, we cannot rule out a certain selection bias considering that readers were rertuied via an open call to ESGAR members (with a specific interest in rectal cancer). Finally, our results should be interpreted with some caution as we have shown that response, and corresponding performance to predict response, was influenced by variations in the interval between CRT and surgery/W&W. Prolonging the interval between CRT and surgery is a known factor that generally results in higher response rates[34-38]. Though variations were small (mean interval between CRT and surgery/W&W was 11 weeks with a standard deviation of 2.5 weeks), a confounding effect could nevertheless not be avoided in this retrospective study setting.
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