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Open access

Ashley K Clift, Omar Faiz, Robert Goldin, John Martin, Harpreet Wasan, Marc-Olaf Liedke, Erik Schloericke, Anna Malczewska, Guido Rindi, Mark Kidd, Irvin M Modlin and Andrea Frilling

Neuroendocrine tumours (NET) are clinically challenging due to their unpredictable behaviour. Nomograms, grading and staging systems are predictive tools with multiple roles in clinical practice, including patient prognostication. The NET nomogram allocates scores for various clinicopathological parameters, calculating percentage estimates for 5- and 10-year disease-specific survival of patients with small bowel (SB) NET. We evaluated the clinical utility of three prognostic systems in 70 SB NET patients: the NET nomogram, the World Health Organisation (WHO)/European Neuroendocrine Tumour Society (ENETS) grading system and the American Joint Commission on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) TNM staging method. Using Kaplan–Meier methodology, neither the WHO/ENETS grade (P = 0.6) nor the AJCC/UICC stage (P = 0.276) systems demonstrated significant differences in patient survival in the cohort. The NET nomogram was well calibrated to our data set, displaying favourable prediction accuracy. Harrel’s C-index for the nomogram (a measure of predictive power) was 0.65, suggesting good prediction ability. On Kaplan–Meier analyses, there were significant differences in patient survival when stratified into nomogram score-based risk groups: low-, medium- and high-risk tumours were associated with median estimated survivals of 156, 129 and 112 months, respectively (P = 0.031). Our data suggest that a multivariable analysis-based NET nomogram may be clinically useful for patient survival prediction. This study identifies the limitations of the NET nomogram and the imperfections of other currently used single or binary parameter methodologies for assessing neuroendocrine disease prognosis. The future addition of other variables to the NET nomogram will likely amplify the accuracy of this personalised tool.

Open access

Logan Mills, Panagiotis Drymousis, Yogesh Vashist, Christoph Burdelski, Andreas Prachalias, Parthi Srinivasan, Krishna Menon, Corina Cotoi, Saboor Khan, Judith Cave, Thomas Armstrong, Martin O Weickert, Jakob Izbicki, Joerg Schrader, Andreja Frilling, John K Ramage and Raj Srirajaskanthan

Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs. The aim of this study was to characterise the prevalence of malignant features and identify any useful predictive variables in a surgically resected cohort of pNETs. 418 patients with pNETs were identified from 5 NET centres. Of these 227 were included for main analysis of tumour characteristics. Mean age of patients was 57 years, 47% were female. The median follow-up was 48.2 months. Malignant features were identified in 38% of ≤2 cm pNETs. ROC analysis showed that the current cut-off of 20 mm had a sensitivity of 84% for malignancy. The rate of malignant features is in keeping with other surgical series and challenges the belief that small pNETs have a low malignant potential. This study does not support a 20 mm size cut-off as being a solitary safe parameter to exclude malignancy in pNETs.

Open access

Gudmundur Johannsson, Martin Bidlingmaier, Beverly M K Biller, Margaret Boguszewski, Felipe F Casanueva, Philippe Chanson, Peter E Clayton, Catherine S Choong, David Clemmons, Mehul Dattani, Jan Frystyk, Ken Ho, Andrew R Hoffman, Reiko Horikawa, Anders Juul, John J Kopchick, Xiaoping Luo, Sebastian Neggers, Irene Netchine, Daniel S Olsson, Sally Radovick, Ron Rosenfeld, Richard J Ross, Katharina Schilbach, Paulo Solberg, Christian Strasburger, Peter Trainer, Kevin C J Yuen, Kerstin Wickstrom, Jens O L Jorgensen and on behalf of the Growth Hormone Research Society

Objective

The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly.

Participants

GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry.

Evidence

Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs.

Consensus process

Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process.

Conclusions

The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.