Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Gerlof D Valk x
  • Refine by Access: All content x
Clear All Modify Search
Open access

Mark J C van Treijen, Catharina M Korse, Wieke H Verbeek, Margot E T Tesselaar, and Gerlof D Valk

Objective

Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied.

Design

The study was a longitudinal validation study of serial NETest measurements – a blood-based gene expression signature – in 132 patients with GEPNETs on therapy or watch-and-wait strategy.

Methods

Serial samples were collected during 46 (range: 6–71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED), stable disease (SD) or progressive disease (PD)).

Results

Consecutive NETest scores fluctuated substantially (range: 0–100) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3–5) and NED subgroups (samples 2–5) compared with baseline results, without changes in imaging. In 82% of untreated patients with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009).

Conclusion

In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.

Open access

Dirk-Jan van Beek, Rachel S van Leeuwaarde, Carolina R C Pieterman, Menno R Vriens, Gerlof D Valk, and the DutchMEN Study Group

Rare diseases pose specific challenges in the field of medical research to provide physicians with evidence-based guidelines derived from studies with sufficient quality. An example of these rare diseases is multiple endocrine neoplasia type 1 (MEN1), which is an autosomal dominant endocrine tumor syndrome with an estimated occurrence rate of 2–3 per 100,000. For this complex disease, characterized by multiple endocrine tumors, it proves difficult to perform both adequate and feasible studies. The opinion of patients themselves is of utmost importance to identify the gaps in the evidence-based medicine regarding clinical care. In the search for scientific answers to clinical research questions, the aim for best available evidence is obvious. Observational studies within patient cohorts, although prone to bias, seem the most feasible study design regarding the disease prevalence. Knowledge and adaptation to all types of bias is demanded in the strive for answers. Guided by our research on MEN1 patients, we elaborate on strategies to identify sufficient patients, to maximize and maintain patient enrolment and to standardize the data collection process. Preferably, data collection is performed prospectively, however, under certain conditions, data storage in a longitudinal retrospective database with a disease-specific framework is suitable. Considering the global challenges on observational research on rare diseases, we propose a stepwise approach from clinical research questions to scientific answers.