Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis.

BACKGROUND: There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. METHODS: Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. RESULTS: We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. CONCLUSIONS: The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.

The RECIST criteria compared to conventional response evaluation after peptide receptor radionuclide therapy in patients with neuroendocrine neoplasms.

OBJECTIVE: The Response Evaluation Criteria In Solid Tumors (RECIST) is the most used radiological method for evaluating response after peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine tumors. This method may give too positive estimates of response in slow growing tumors as it allows a substantial increase in tumor size before patients are classified as having progressive disease. We wanted to compare RECIST with a conventional method in routine use for estimating treatment effect based on defining any unequivocal increase in size of tumor load as progressive disease. We also wanted to investigate whether any differences had clinical implications. METHODS: Patients treated with 177Lutetium-DOTA-octreotate having at least one follow-up radiological response evaluation were included. Radiological examinations were retrospectively evaluated by RECIST and compared to the radiological evaluations performed at regular follow-up examinations. RESULTS: Seventy-nine patients were included, 33 (42%) were women, median age 65 years. The primary tumors was located in the small intestine in 35 (44%) and the in the pancreas in 27 (34%) of the patients. Indication for treatment was progressive disease in 71 (90%) patients. Based on RECIST, 67 (85%) patients had objective response or stable disease as best effect versus 59 (75%) patients based on the conventional method (p < 0.001). Median progression free survival was 33 months estimated by RECIST and 28 months estimated with the conventional method (p < 0.001). Eight (10%) patients received tumor-targeted therapy due to progressive disease based on the conventional method while still having stable disease according to RECIST. CONCLUSION: Response evaluation after PRRT with RECIST gave more positive estimates for treatment effects compared to a method where any equivocal change in tumor load was regarded as significant. These differences had clinical implications.