European Radiology

, Volume 28, Issue 12, pp 5250–5257 | Cite as

CT evaluation of response in advanced gastroenteropancreatic neuroendocrine tumors treated with long-acting-repeatable octreotide: what is the optimal size variation threshold?

  • Yanji Luo
  • Jie Chen
  • Bingqi Shen
  • Meng Wang
  • Huasong Cai
  • Ling Xu
  • Luohai Chen
  • Minhu Chen
  • Zi-Ping LiEmail author
  • Shi-Ting FengEmail author



To identify a reliable early indicator of deriving progression-free survival (PFS) benefit in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with octreotide long-acting repeatable (LAR).


We investigated the images of 50 patients with well-differentiated advanced GEP-NETs treated with LAR octreotide and underwent baseline and follow-up thoracic, abdominal, and pelvic computed tomography. Receiver-operating characteristic (ROC) analysis and the Kaplan-Meier method were used to identify the optimal threshold to distinguish between those with and without significant improvement of PFS.


The optimal threshold for determining a response to octreotide LAR was -10% ΔSLD, with a sensitivity and specificity of 85.7% and 80%, respectively. At this threshold, 19 patients were responders and 31 were non-responders; the median PFS was 20.2 and 7.6 months in responders and non-responders (hazard ratio, 2.66; 95% confidence interval, 1.32–5.36).


A 10% shrinkage in tumor size is an optimal early predictor of response to octreotide LAR in advanced GEP-NETs.

Key points

Octreotide LAR can significantly prolong PFS among patients with well-differentiated advanced GEP-NETs.

No optimal tumor size-based response criteria are reported in GEP-NETs with octreotide.

Ten percent tumor shrinkage is a reliable indicator of the response to octreotide for advanced GEP-NETs.


Neuroendocrine tumors Octreotide Progression-free survival Response Evaluation Criteria in Solid Tumors Tomography, spiral computed 



Computed tomography


Gastroenteropancreatic neuroendocrine tumors

Octreotide LAR

Octreotide long-acting repeatable


Progressive disease


Progression-free survival


Partial response


Response Evaluation Criteria in Solid Tumors

ROC curve

Receiver-operating characteristic curve


Stable disease


Sum of the longest diameters


Somatostatin analogs


Transhepatic arterial chemotherapy and embolization


Well-differentiated advanced gastroenteropancreatic neuroendocrine tumors


Change in the sum of the longest tumor diameters



National Natural Science Foundation of China (81771908,81571750, 81770654), National Key Research and Development Program of China (2017YFC0113402), Guangzhou Science and Technology Foundation (201804010078). Natural Science Foundation of Guangdong Province (2015A030313043).

Compliance with ethical standards


The scientific guarantor of this publication is Dr. Shi-Ting Feng.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Ms. Fangjing Zhou (expert in statistics, Sun Yat-Sen University) kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• diagnostic or prognostic study

• performed at one institution

Supplementary material

330_2018_5512_MOESM1_ESM.pdf (105 kb)
Figure 5 (PDF 104 kb)


  1. 1.
    Yao JC, Hassan M, Phan A et al (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063–3072CrossRefGoogle Scholar
  2. 2.
    Gustafsson BI, Kidd M, Modlin IM (2008) Neuroendocrine tumors of the diffuse neuroendocrine system. Curr Opin Oncol 20:1–12CrossRefGoogle Scholar
  3. 3.
    Ramage JK, Ahmed A, Ardill J et al (2012) Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 61:6–32CrossRefGoogle Scholar
  4. 4.
    Vinik AI, Anthony L, Boudreaux JP et al (2010) Neuroendocrine tumors: a critical appraisal of management strategies. Pancreas 39:801–818CrossRefGoogle Scholar
  5. 5.
    Ballian N, Loeffler AG, Rajamanickam V, Norstedt PA, Weber SM, Cho CS (2009) A simplified prognostic system for resected pancreatic neuroendocrine neoplasms. HPB (Oxford) 11:422–428CrossRefGoogle Scholar
  6. 6.
    Schimmack S, Svejda B, Lawrence B, Kidd M, Modlin IM (2011) The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors. Langenbecks Arch Surg 396:273–298CrossRefGoogle Scholar
  7. 7.
    Kocha W, Maroun J, Kennecke H et al (2010) Consensus recommendations for the diagnosis and management of well-differentiated gastroenterohepatic neuroendocrine tumours: a revised statement from a Canadian National Expert Group. Curr Oncol 17:49–64CrossRefGoogle Scholar
  8. 8.
    Fazio N, Spada F, Giovannini M (2013) Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): a critical view. Cancer Treat Rev 39:270–274CrossRefGoogle Scholar
  9. 9.
    Strosberg JR, Fine RL, Choi J et al (2011) First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 117:268–275CrossRefGoogle Scholar
  10. 10.
    Raymond E, Dahan L, Raoul JL et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513CrossRefGoogle Scholar
  11. 11.
    Benavent M, de Miguel MJ, Garcia-Carbonero R (2012) New targeted agents in gastroenteropancreatic neuroendocrine tumors. Target Oncol 7:99–106CrossRefGoogle Scholar
  12. 12.
    Yang TX, Chua TC, Morris DL (2012) Radioembolization and chemoembolization for unresectable neuroendocrine liver metastases—a systematic review. Surg Oncol 21:299–308CrossRefGoogle Scholar
  13. 13.
    Akyildiz HY, Mitchell J, Milas M, Siperstein A, Berber E (2010) Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery 148:1288–1293CrossRefGoogle Scholar
  14. 14.
    Atwell TD, Charboneau JW, Que FG et al (2005) Treatment of neuroendocrine cancer metastatic to the liver: the role of ablative techniques. Cardiovasc Intervent Radiol 28:409–421CrossRefGoogle Scholar
  15. 15.
    Rossi RE, Burroughs AK, Caplin ME (2014) Liver transplantation for unresectable neuroendocrine tumor liver metastases. Ann Surg Oncol 21:2398–2405CrossRefGoogle Scholar
  16. 16.
    Jann H, Denecke T, Koch M, Pape UF, Wiedenmann B, Pavel M (2013) Impact of octreotide long-acting release on tumour growth control as a first-line treatment in neuroendocrine tumours of pancreatic origin. Neuroendocrinology 98:137–143CrossRefGoogle Scholar
  17. 17.
    Attanasio R, Mainolfi A, Grimaldi F et al (2008) Somatostatin analogs and gallstones: a retrospective survey on a large series of acromegalic patients. J Endocrinol Invest 31:704–710CrossRefGoogle Scholar
  18. 18.
    Rinke A, Müller HH, Schade-Brittinger C et al (2009) PROMID Study Group. Placebo controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27:4656–4663CrossRefGoogle Scholar
  19. 19.
    Caplin ME, Pavel M, Ruszniewski P (2014) Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371:1556–1557CrossRefGoogle Scholar
  20. 20.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216CrossRefGoogle Scholar
  21. 21.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefGoogle Scholar
  22. 22.
    Chen HX, Rubinstein LV, Shankar LK, Abrams JS (2014) Are we ready for the 10% solution? Oncologist 19:439–440CrossRefGoogle Scholar
  23. 23.
    Krajewski KM, Franchetti Y, Nishino M et al (2014) 10% tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study. Oncologist 19:507–514CrossRefGoogle Scholar
  24. 24.
    Thiam R, Fournier LS, Trinquart L et al (2010) Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib. Ann Oncol 21:936–941CrossRefGoogle Scholar
  25. 25.
    Krajewski KM, Guo M, Van den Abbeele AD et al (2011) Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol 59:856–862CrossRefGoogle Scholar
  26. 26.
    Oudard S, Thiam R, Fournier LS et al (2012) Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study. Eur J Cancer 48:1512–1518CrossRefGoogle Scholar
  27. 27.
    Monsky WL, Raptopoulos V, Keogan MT et al (2004) Reproducibility of linear tumor measurements using PACS: comparison of caliper method with edge-tracing method. Eur Radiol 14:519–525CrossRefGoogle Scholar
  28. 28.
    Krajewski KM, Fougeray R, Bellmunt J et al (2012) Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine. Eur J Cancer 48:1495–1502CrossRefGoogle Scholar
  29. 29.
    Cremolini C, Loupakis F, Antoniotti C et al (2015) Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol 26:1188–1894CrossRefGoogle Scholar
  30. 30.
    Krajewski KM, Nishino M, Ramaiya NH, Choueiri TK (2015) RECIST 1.1 compared with RECIST 1.0 in patients with advanced renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. AJR Am J Roentgenol 204:W282–W828CrossRefGoogle Scholar
  31. 31.
    Erasmus JJ, Gladish GW, Broemeling L et al (2003) Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J Clin Oncol 21:2574–2582CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Yanji Luo
    • 1
  • Jie Chen
    • 2
  • Bingqi Shen
    • 1
  • Meng Wang
    • 1
  • Huasong Cai
    • 1
  • Ling Xu
    • 3
  • Luohai Chen
    • 2
  • Minhu Chen
    • 2
  • Zi-Ping Li
    • 1
    Email author
  • Shi-Ting Feng
    • 1
    Email author
  1. 1.Department of Radiology, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Gastroenterology, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  3. 3.Faculty of Medicine and DentistryUniversity of Western AustraliaPerthAustralia

Personalised recommendations