Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

Abstract

PurposeTo review the response and outcomes of 177Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression.MethodsA total of 68 patients (39 men; 17 – 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression.ResultsOf those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 – 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival.ConclusionA high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was associated with improved overall survival. Patients with a primary pancreatic site and larger lesions (>5 cm) appeared to have lower objective response rates and may need a more aggressive treatment approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-014-2788-5) contains supplementary material, which is available to authorized users.

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

“…This approach has included studies with infusion of 5-fluorouracil or administration of its oral pro-drug, capecitabine [47,48,49,50,51], and a further study using capecitabine and temozolomide [52]. A randomized controlled trial of the latter combination is currently underway in Australia, whereas the former is being tested in the Netherlands.…”

“…Accordingly, new lesions as an indicator of progression or disappearance of prior lesions may be more sensitively detected by SSTR imaging than by CT. While morphologic regression is clearly desirable, more patients can be demonstrated to have responded by reduction in the extent or number of lesions on SSTR imaging and the prognostic value of such response is similar [50]. The availability of serum biomarkers like chromogranin A or other specific hormones also provides an important means to assess response.…”

Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine

“…Unfortunately, the animal tumor model used is not representative of the nature of tumors in humans (heterogeneous vs. homogeneous distributions of somatostatin receptors). Additionally, there are currently no randomized trial data comparing the combination of 90 Y PRRT and 177 Lu PRRT with 177 Lu PRRT alone, leaving the actual benefit of this combination of radionuclides in humans with GEP-NETs unknown, although potential efficacy has been reported (55,56 (58)(59)(60).…”

Exploiting induced senescence in intestinal organoids to drive enteroendocrine cell expansion

“…New approaches that employ isotopes that target cytotoxic insult to the tumour while also permitting PET imaging is an exciting development in oncology (13,14). Nevertheless, this study by Basak et al, indicating that enteroendocrine cells arise from Lgr5+ve cells that can be in a quiescent state may also inform future approaches and the opportunity to model this biology using organoids.…”