Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P &lt; 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.</p

Machine learning versus logistic regression for the prediction of complications after pancreatoduodenectomy

BACKGROUND: Machine learning is increasingly advocated to develop prediction models for postoperative complications. It is, however, unclear if machine learning is superior to logistic regression when using structured clinical data. Postoperative pancreatic fistula and delayed gastric emptying are the two most common complications with the biggest impact on patient condition and length of hospital stay after pancreatoduodenectomy. This study aimed to compare the performance of machine learning and logistic regression in predicting pancreatic fistula and delayed gastric emptying after pancreatoduodenectomy. METHODS: This retrospective observational study used nationwide data from 16 centers in the Dutch Pancreatic Cancer Audit between January 2014 and January 2021. The area under the curve of a machine learning and logistic regression model for clinically relevant postoperative pancreatic fistula and delayed gastric emptying were compared. RESULTS: Overall, 799 (16.3%) patients developed a postoperative pancreatic fistula, and 943 developed (19.2%) delayed gastric emptying. For postoperative pancreatic fistula, the area under the curve of the machine learning model was 0.74, and the area under the curve of the logistic regression model was 0.73. For delayed gastric emptying, the area under the curve of the machine learning model and logistic regression was 0.59. CONCLUSION: Machine learning did not outperform logistic regression modeling in predicting postoperative complications after pancreatoduodenectomy

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

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.</p

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

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.</p

Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models

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

The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment

OBJECTIVES: Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). BACKGROUND: RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. METHODS: Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. RESULTS: A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of &gt;40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease ( = 0.015), while RECIST1.1 was not prognostic ( = 0.821). CONCLUSIONS: TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

Abstract: 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 center dot Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. center dot Automatic models can accurately segment tumors in patients with colorectal liver metastases. center dot Total tumor volume can be accurately calculated based on automatic segmentations

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

Abstract 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 Abstrac

The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment

Objectives:. Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). Background:. RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. Methods:. Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. Results:. A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease (P = 0.015), while RECIST1.1 was not prognostic (P = 0.821). Conclusions:. TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM