Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer

Background First line chemotherapy is effective in 75 to 80% of patients with metastatic colorectal cancer (mCRC). We studied whether microRNA (miR) expression profiles can predict treatment outcome for first line fluoropyrimidine containing systemic therapy in patients with mCRC. Methods MiR expression levels were determined by next generation sequencing from snap frozen tumor samples of 88 patients with mCRC. Predictive miRs were selected with penalized logistic regression and posterior forward selection. The prediction co-efficients of the miRs were re-estimated and validated by real-time quantitative PCR in an independent cohort of 81 patients with mCRC. Results Expression levels of miR-17-5p, miR-20a-5p, miR-30a-5p, miR-92a-3p, miR-92b-3p and miR-98-5p in combination with age, tumor differentiation, adjuvant therapy and type of systemic treatment, were predictive for clinical benefit in the training cohort with an AUC of 0.78. In the validation cohort the addition of the six miR signature to the four clinicopathological factors demonstrated a significant increased AUC for predicting treatment response versus those with stable disease (SD) from 0.79 to 0.90. The increase for predicting treatment response versus progressive disease (PD) and for patients with SD versus those with PD was not significant. in the validation cohort. MiR-17-5p, miR-20a-5p and miR-92a-3p were significantly upregulated in patients with treatment response in both the training and validation cohorts. Conclusion A six miR exp

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

Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient

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. Graphical Abstract: [Figure not available: see fulltext.]

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 < 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