“…5). Two studies have also shown that the use of LuTate as salvage treatment is effective and safe in patients with progressive disease after initial benefit from induction treatment [22, 23]. Fig.…”
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.
“…5). Two studies have also shown that the use of LuTate as salvage treatment is effective and safe in patients with progressive disease after initial benefit from induction treatment [22, 23]. Fig.…”
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.
“…In our experience, PRLT can be safely repeated, inducing regression of the disease again (Fig. 5) (27). The maximum tolerable dose of PRLT has not yet been systematically studied.…”
A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with 68 Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with 177 Lu-PSMA ligands. 68 Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring. Our comprehensive experience over the last 3 years using different radioligands indicates that PRLT is highly effective for the treatment of mCRPC, even in advanced cases, and potentially lends a significant benefit to overall and progression-free survival. Additionally, significant improvement in clinical symptoms and excellent palliation of pain can be achieved.
“…One of the German groups [9] retrospectively analysed 33 patients who underwent re-treatment with 177 Lu-DOTATATE (mean cumulative activity 17.3 GBq, range 8-33 GBq) after initial response to a first treatment period of PRRT. The total administered activity of both treatment periods amounted to a mean of 44.3 GBq (range 30-83.7 GBq).…”
# Springer-Verlag Berlin Heidelberg 2015 Radiolabelled peptides transport radioactivity to a specific receptor expressed on the cell surface. In the last decade treatment strategies with radiolabelled somatostatin analogues have shown convincing results for neuroendocrine tumour (NET) patients with high-density expression of somatostatin receptors. The radiolabelled somatostatin receptor agonists 90 Y-DOTA-D-Phe 1 -Tyr 3 -octreotide (DOTATOC), 177 Lu-DOTA-D-Phe 1 -Tyr 3 -Thr 8 -octreotide (DOTATATE) and 177 Lu-DOTATOC are applied intravenously, are internalized into the tumour cell via the receptor and irradiate the tumour with β-emission of the coupled radioisotope. The availability of different radioisotopes potentially allows tailoring peptide receptor radionuclide therapy (PRRT) to the individual patient. With its maximum range of 1.1 cm, 90 Y is able to deposit about 60 % of its energy in a 1-cm tumour lesion, whereas the 0.16 cm range of 177 Lu can deposit about 95 % of its energy in a 1-cm lesion. This suggests that 90 Y-coupled peptides would work better for larger lesions and 177 Lu-coupled peptides for smaller lesions [1].For metastatic NET patients treatment options are limited, and relapses occur after a certain time in many patients. In general, PRRT is used after failing first-line medical therapy. The high absorbed tumour dose following PRRT may lead to partial or even complete objective response. There are different research PRRT protocols in use with either standard dose or individualized therapy with a variable number of cycles. The BPRRT regimen^usually consists of several treatment cycles where the radiolabelled somatostatin analogue is administered intravenously together with amino acids for kidney protection. An interval of about 10 weeks is kept between two radioactive treatment cycles. The long-lasting form of the somatostatin analogues octreotide [2] or lanreotide [3] can be applied between the treatment cycles but should be at least 4 weeks apart from the radioactive cycle. A Btreatment period^consists of several radioactive cycles. As we treat relapsing patients in advanced stages stabilization of the metastatic disease is considered as the potential treatment goal. Documented overall response to treatment in gastroenteropancreatic NETs, neuroectodermal tumours (such as paraganglioma or phaeochromocytoma) or lung NETs is~80 %, stable disease/ minor response~55 %, complete/partial remission~25 % and progressive disease~20 %. The side effects to kidney or bone marrow are usually mild. Taking the data together, the median progression-free survival (PFS) amounts to~2 years (~5 years in the responding groups and to less than 1 year in the nonresponding progressive group) which is significantly longer than historical control groups without this procedure.The joint International Atomic Energy Agency (IAEA), European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Medical Imaging (SNMMI) guideline for PRRT can be a good starting point for initial decision-making fo...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
