Purpose: Advanced medical image analytics is increasingly used to predict clinical outcome in patients diagnosed with gastrointestinal tumors. This review provides an overview on the value of radiomics in predicting response to treatment in patients with gastrointestinal tumors. Methods: A systematic review was conducted, according to PRISMA guidelines. The protocol was prospectively registered (PROSPERO: CRD42019128408). PubMed, Embase, and Cochrane databases were searched. Original studies reporting on the value of radiomics in predicting response to treatment in patients with a gastrointestinal tumor were included. A narrative synthesis of results was conducted. Results were stratified by tumor type. Quality assessment of included studies was performed, according to the radiomics quality score. Results: The comprehensive literature search identified 1360 unique studies, of which 60 articles were included for analysis. In 37 studies, radiomics models and individual radiomic features showed good predictive performance for response to treatment (area under the curve or accuracy > 0.75). Various strategies to construct predictive models were used. Internal validation of predictive models was often performed, while the majority of studies lacked external validation. None of the studies reported predictive models implemented in clinical practice. Conclusion: Radiomics is increasingly used to predict response to treatment in patients suffering from gastrointestinal cancer. This review demonstrates its great potential to help predict response to treatment and improve patient selection and early adjustment of treatment strategy in a non-invasive manner.

Background: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). Methods: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. Results: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95–0.96) and 0.80 (IQR 0.67–0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29–0.76) for tumor segmentation. Conclusions: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. Relevance statement: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist’s workload and increasing accuracy and consistency. Key points: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations. Graphical

To better select patients with colorectal liver metastases (CRLM) for an optimal selection of treatment strategy (i.e. local, systemic or combined treatment) new prognostic models are warranted. In the last decade, radiomics has emerged as a field to create predictive models based on imaging features. This systematic review aims to investigate the current state and potential of radiomics to predict clinical outcomes in patients with CRLM. A comprehensive literature search was conducted in the electronic databases of PubMed, Embase, and Cochrane Library, according to PRISMA guidelines. Original studies reporting on radiomics predicting clinical outcome in patients diagnosed with CRLM were included. Clinical outcomes were defined as response to systemic treatment, recurrence of disease, and survival (overall, progression-free, disease-free). Primary outcome was the predictive performance of radiomics. A narrative synthesis of the results was made. Methodological quality was assessed using the radiomics quality score. In 11 out of 14 included studies, radiomics was predictive for response to treatment, recurrence of disease, survival, or a combination of outcomes. Combining clinical parameters and radiomic features in multivariate modelling often improved the predictive performance. Different types of individual features were found prognostic. Noticeable were the contrary levels of heterogeneous and homogeneous features in patients with good response. The methodological quality as assessed by the radiomics quality score varied considerably between studies. Radiomics appears a promising non-invasive method to predict clinical outcome and improve personalized decision-making in patients with CRLM. However, results were contradictory and difficult to compare. Standardized prospective studies are warranted to establish the added value of radiomics in patients with CRLM.

Assessment of morphologic tumor response on CT scans of patients with initially unresectable colorectal liver metastases treated with systemic therapy resulted in considerable interobserver variabi... Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morpholo...

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62–0.92), 0.77 (95%CI 0.64–0.90), 0.72 (95%CI 0.57–0.87), and 0.86 (95%CI 0.76–0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47–0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.

This study aimed to assess whether total tumor volume (TTV) outperforms RECIST1.1 for treatment response assessment in patients with colorectal liver metastases (CRLM), and to investigate TTV as a predictive biomarker for the optimal systemic treatment regimen for individual patients with initially unresectable CRLM. Patients with initially unresectable liver-only CRLM from the phase 3 CAIRO5 trial (NCT02162563) were included. All patients received induction systemic treatment. Baseline TTV and changes in TTV and RECIST1.1 in response to systemic treatment were calculated using the CT scans before systemic treatment and at first follow-up, and were assessed for their prognostic and predictive value with multivariable Cox regression models. Results In total, 425 patients were included. In multivariable analyses, baseline TTV (adjusted HR [aHR] for 100 mL vs 10 mL, 2.44 [95 % CI, 1.25-4.76]; P = 0.006) and relative change in TTV were the strongest predictors for OS (aHR for 0 % change vs 50 % decrease, 2.57 [1.83-3.60]; P < 0.0001). In contrast, RECIST1.1 was not independently associated with OS (aHR for partial response vs progressive disease, 0.63 [95 % CI, 0.33-1.20]). Higher baseline TTV predicted a stronger treatment benefit of FOLFOX-/FOLFIRI-bevacizumab vs FOLFOX-/FOLFIRI-panitumumab on OS (P_interaction=0.017). This study demonstrates that TTV (i) outperforms traditional risk factors for OS prognostication, and (ii) may be a more accurate and sensitive treatment response assessment method compared to the currently used RECIST1.1 system in patients with initially unresectable CRLM. Moreover, TTV assessment is a promising approach for individualized clinical decision-making between bevacizumab and panitumumab.