Published online Jul 7, 2020. doi: 10.3748/wjg.v26.i25.3686
Peer-review started: March 9, 2020
First decision: March 31, 2020
Revised: June 4, 2020
Accepted: June 17, 2020
Article in press: June 17, 2020
Published online: July 7, 2020
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) and pancreas (P-NETs). The majority of patients who are diagnosed with GEP-NETs have metastatic disease. Despite this, systemic therapies provide a 5-year survival rate of about 75% for patients with GI-NETs and > 60% for patients with P-NETs.
Health related quality of life (HRQoL) is an increasingly important concept, reflecting the patients’ perspective in conjunction with the disease presentation, severity, and treatment. Although not curative, long-term therapeutic options are available for patients with GEP-NETs to provide symptomatic relief, and these can even slow down and stabilise disease for multiple years. Since patients can live many years by managing their disease in this way, understanding the impact of treatment on GEP-NETs patients’ HRQoL is paramount especially given the indolent course the disease may take in patients.
The aim of this study was to perform a systematic review to assess the HRQoL of patients with inoperable metastatic GEP-NETs undergoing various treatments in order to uncover areas for future research. This systematic literature review is a response to the increased importanceof assessing HRQoL with validated patient-reported outcome instruments for which the minimal important difference has been defined.
The systematic review performed here adhered to the established international guidelines for conducting systematic reviews. A search strategy was developed and refined to recover relevant publications reporting HRQoL data for adult patients with GEP-NETs. Data were extracted from every record returned by the literature search that met the inclusion criteria of the study.
A total of 42 studies met the inclusion criteria of the study. The EORTC QLQ-C30 and gastrointestinal GI-NET module (QLQ-GI.NET21) were the most used HRQoL instruments, exhibiting a range of outcomes compared to baseline for the specific interventions.
The worst HRQoL observed at baseline were related to the following symptoms: Nausea and vomiting (4.1–20.0), insomnia (11.0–38.6), appetite loss (9.2–27.8), constipation (0–24.4) and financial difficulties (6.0–23.6). Diarrhoea demonstrated a wide range of mean values (16.7–78.3), which can be attributed to the heterogeneity of involved GEP-NET patients.
The average value for the baseline global health score had a range of 56–70. Where change in the EORTC QLQ-C30 global health score could be calculated from baseline scores, five studies demonstrated a significant trend towards an improved score. Treatment of GEP-NETs with 177Lu-DOTATATE consistently improved global health score compared to baseline and increased time-to-deterioration, i.e. time until HRQoL worsens by at least 10 points for each domain (e.g. global health, physical functioning). The Phase III NETTER-1 study resulted in time-to-deterioration curves consistent with the curves for progression free survival for 177Lu-DOTATATE. However, the EORTC QLQ-C30 and QLQ-GINET21 have not been validated, and the minimal important differences have not yet been defined, specifically for GI-NET and P-NET patients.
Study and patient heterogeneity, small sample sizes and limited methodological quality in terms of assessing HRQoL has impaired definitive statements being made regarding the impact of the various treatment options for GEP-NETs in terms of HRQoL. A notable finding was that PRRT can delay the time to worsening of HRQoL in GEP-NET patients. However, validation of EORTC QLQ-C30 and GINET21 specifically for GI-NET and P-NET patients and the definitions of minimal important difference and clinical thresholds are still lacking for these patients. As such, further research is necessary in order to offer a benchmark for interpreting the clinical importance of differences in HRQoL domain scores between treatment groups or changes in these scores over time in conjunction with different treatment modalities.
Further research is necessary in order to offer a benchmark for interpreting the clinical importance of differences in HRQoL domain scores over time and between treatment groups.