Development of a disease-specific quality of life questionnaire module for patients with gastrointestinal neuroendocrine tumours

Davies, Amy; Larsson, Gunilla; Ardill, Joy; Friend, Elizabeth; Jones, L; Falconi, Massimo; Bettini, Rossella; Koller, Michael; Sezer, Orhan; Fleissner, Claudia; Taal, Babs G.; Blazeby, Jane M; Ramage, John

doi:10.1016/j.ejca.2005.10.025

Cited by 66 publications

(48 citation statements)

References 31 publications

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“…These differences in synthesis were reflected in secretion studies. Thus, basal 5-HT secretion was significantly higher (increased 2- to 3-fold) in KRJ-I than BON at both 60 min and 24 h. Midgut (EC cell) NETs usually secrete high levels of 5-HT in contrast to foregut NET which very rarely secrete 5-HT [55, 56]. The lower and inconsistent levels of 5-HT secretion from the BON cell line therefore argue that this cell system has not only different mechanisms of synthesis but also a variable, non-EC cell phenotype.…”

Section: Discussionmentioning

confidence: 99%

KRJ-I and BON Cell Lines: Defining an Appropriate Enterochromaffin Cell Neuroendocrine Tumor Model

et al. 2009

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Background: Neuroendocrine tumors (NETs) of the gastrointestinal (GI) system are increasing in incidence with minimal improvement in prognosis. Although the cell of origin has been identified as the enterochromaffin (EC) cell, its secretory and proliferative regulation has not been defined at a mechanistic level. To date, the BON cell line has been the most widely used in vitro EC cell model despite its pancreatic origin. Using whole-genome mathematical analysis as well as secretory and proliferative studies, we compared the BON cell line to the small intestine (SI) EC cell-derived NET cell line, KRJ-I, to assess individual cell line validity and applicability for the investigation of GI-NET disease. Methods and Results: Principal component analysis and ANOVA of KRJ-I and BON transcriptomes (U133 Plus 2) identified substantially different (<10%) overlap in transcripts with minimal (R² = 0.24) correlation in gene expression profiles. RT-PCR detected large variability (>12%) in neuroendocrine (NE) marker transcripts in the BON cell line and the absence of Tph-2, DDC, TGFβR2, and M3 transcripts in KRJ-I. The KRJ-I cell line secreted serotonin (5-HT) in response to isoproterenol (EC₅₀ = 100 nM), noradrenaline (EC₅₀ = 1.7 nM), and pituitary adenylate cyclase (PACAP, EC₅₀ = 0.03 nM). Cholecystokinin (IC₅₀ = 430 nM), somatostatin (IC₅₀ = 400 nM), acetylcholine (IC₅₀ = 3.7 nM), and γ-aminobutyric acid A (GABA_A, IC₅₀ = 2 nM) all inhibited 5-HT release, while gastrin and bombesin had no effect. 5-HT secretion in the BON cell line was stimulated by isoproterenol (EC₅₀ = 900 nM), noradrenaline (EC₅₀ = 20 nM), cholecystokinin (EC₅₀ = 130 nM), PACAP (EC₅₀ = 0.12 nM), bombesin (EC₅₀ = 15 nM), and acetylcholine (EC₅₀ = 0.2 nM). It was inhibited by somatostatin (IC₅₀ = 300 nM) but not GABA_A. KRJ-I responded with proliferation to connective tissue growth factor (CTGF, EC₅₀ = 0.002 ng/ml), transforming growth factor-α (TGFα, EC₅₀ = 0.63 ng/ml) and transforming growth factor-β (TGFβ, EC₅₀ = 0.63 ng/ml). Epidermal growth factor (EGF) and somatostatin had no significant effect. BON cell proliferation was stimulated only by EGF and TGFα (EC₅₀ = 15.8 and 10 ng/ml). TGFβ (IC₅₀ = 0.16 ng/ml), MZ-4-147 (IC₅₀ = 0.5 nM), and BIM23A761 (IC₅₀ = 0.06 nM) all inhibited proliferation. CTGF and somatostatin had no effect. Conclusion: KRJ-I and BON cell lines demonstrate substantial differences in gene level transcripts, inconsistent receptor profile expression, wide variability in NE marker transcript levels, and significantly differential proliferative and secretory responses. Given the EC cell origin of KRJ-I, these results provide evidence that the BON cell line does not represent an EC cell system and is not a valid study model of (carcinoid) EC cell-derived NET.

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Section: Discussionmentioning

confidence: 99%

KRJ-I and BON Cell Lines: Defining an Appropriate Enterochromaffin Cell Neuroendocrine Tumor Model

et al. 2009

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“…The QLQ-C30 questionnaire has not been validated as a surrogate marker of tumor progression (Raymond et al 2011). QLQ-GINET21 includes items specific to NET patients and has been recently shown to change in response to expected clinical evolution after therapy (Davies et al 2006, Yadegarfar et al 2013. Thus, correlation between variation of the standardized qualityof-life assessment and tumor evolution should be examined for NET patients.…”

Section: Radiopharmaceutical Imaging Techniquesmentioning

confidence: 99%

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Mestier¹,

Dromain²,

d’Assignies³

et al. 2013

Endocrine-Related Cancer

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Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.

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“…15 Used together with a more general quality-of-life questionnaire, this may be a useful tool in future trials. Randomized, controlled studies of novel agents in patients with hormonal syndrome refractory to somatostatin analogs, using patient-reported outcome measures, are appropriate and should be feasible.…”

mentioning

confidence: 99%

Future Directions in the Treatment of Neuroendocrine Tumors: Consensus Report of the National Cancer Institute Neuroendocrine Tumor Clinical Trials Planning Meeting

Kulke

Siu

Tepper

et al. 2011

JCO

275

227

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Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals. The recent completion of several phase III studies, including those evaluating octreotide, sunitinib, and everolimus, has demonstrated that rigorous evaluation of novel agents in this disease is both feasible and can lead to practice-changing outcomes. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies for the US cooperative group program. Emphasis was placed on the development of well-designed clinical trials with clearly defined efficacy criteria. Key recommendations include the evaluation of pancreatic NET separately from NETs of other sites and the exclusion of patients with poorly differentiated histologies from trials focused on low-grade histologies. Studies evaluating novel agents for the control of hormonal syndromes should avoid somatostatin analog washout periods when possible and should include quality-of-life end points. Because of the observed long survival after progression of many patients, progression-free survival is recommended as a feasible and relevant primary end point for both phase III studies and phase II studies where a delay in progression is expected in the absence of radiologic responses. J Clin

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Development of a disease-specific quality of life questionnaire module for patients with gastrointestinal neuroendocrine tumours

Cited by 66 publications

References 31 publications

KRJ-I and BON Cell Lines: Defining an Appropriate Enterochromaffin Cell Neuroendocrine Tumor Model

KRJ-I and BON Cell Lines: Defining an Appropriate Enterochromaffin Cell Neuroendocrine Tumor Model

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Future Directions in the Treatment of Neuroendocrine Tumors: Consensus Report of the National Cancer Institute Neuroendocrine Tumor Clinical Trials Planning Meeting

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