Koert F D Kuhlmann1, Margot E T Tesselaar2, Sonja Levy3, James D Arthur4, Melissa Banks4, Niels F M Kok1, Stephen W Fenwick4, Rafael Diaz-Nieto4, Monique E van Leerdam5, Daniel J Cuthbertson6,7, Gerlof D Valk8. 1. Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 2. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. so.levy@nki.nl. 4. Department of Surgery, Liverpool University Hospital NHS Foundation Trust, Liverpool, UK. 5. Department of Gastroenterologic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Institute of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK. 7. Department of Endocrinology, Liverpool University Hospital NHS Foundation Trust, Liverpool, UK. 8. Department of Endocrine Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Abstract
INTRODUCTION: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. OBJECTIVE: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. METHODS: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). RESULTS: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I-III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. CONCLUSION: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.
INTRODUCTION: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. OBJECTIVE: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. METHODS: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using 'institute' as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). RESULTS: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I-III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. CONCLUSION: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.
Authors: Md Jamal Uddin; Rolf H H Groenwold; Mohammed Sanni Ali; Anthonius de Boer; Kit C B Roes; Muhammad A B Chowdhury; Olaf H Klungel Journal: Int J Clin Pharm Date: 2016-04-18
Authors: Alexandra Gangi; Nicholas Manguso; Jun Gong; Jessica S Crystal; Shirley C Paski; Andrew E Hendifar; Richard Tuli Journal: Ann Surg Oncol Date: 2020-05-11 Impact factor: 5.344