scholarly journals Pitfalls in the response evaluation after peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

2017 ◽  
Vol 24 (5) ◽  
pp. 243-251 ◽  
Author(s):  
Tessa Brabander ◽  
Wouter A van der Zwan ◽  
Jaap J M Teunissen ◽  
Boen L R Kam ◽  
Wouter W de Herder ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumour Marker ◽  
Repeated Measurements ◽  
Peptide Receptor ◽  
Anatomical Imaging ◽  
Gastroenteropancreatic Neuroendocrine Tumours

Peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) is a treatment with good results in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEPNETs). However, there are some pitfalls that should be taken into consideration when evaluating the treatment response after PRRT. 354 Dutch patients with GEPNETs who were treated with 177Lu-DOTATATE between March 2000 and December 2011 were retrospectively selected. Liver function parameters and chromogranin A were measured before each therapy and in follow-up. Anatomical imaging was performed before therapy and in follow-up. An increase in aminotransferases by ≥20% compared to baseline was observed in 83 of 351 patients (24%). In patients with an objective response (OR) and stable disease (SD) this increase was observed in 71/297 (24%) and in patients with progressive disease (PD) it was observed in 12/54 patients (22%). An increase in chromogranin A by ≥20% compared to baseline was observed in 76 patients (29%). This was present in 34% of patients who eventually had PD and 27% of patients who had OR/SD. In 70% of patients this tumour marker returned to baseline levels after therapy. An increase in liver enzymes and chromogranin A is not uncommon after PRRT. In the vast majority of patients this will resolve in follow-up. Clinicians should be aware that these changes may occur due to radiation-induced inflammation or disease progression and that repeated measurements over time are necessary to differentiate between the two.

Surgery in combination with peptide receptor radionuclide therapy is effective in metastatic neuroendocrine tumors and is definable by blood gene transcript analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15697-e15697
Author(s):  
Andreja Frilling ◽  
Daniel Kaemmerer ◽  
Mark S. Kidd ◽  
Ashley K Clift ◽  
Justin Stebbing ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Initial Diagnosis ◽  
Gene Transcript ◽  
Transcript Analysis ◽  
Surgical Morbidity ◽  
Eligibility Criteria ◽  
Naive Patient ◽  
Peptide Receptor

e15697 Background: Neuroendocrine tumours (NET) of the pancreas (PNET) or small bowel (SBNET) frequently present with metastases at initial diagnosis, undermining the efficacy of surgical treatment. Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, has been shown to achieve prolonged progression-free survival (PFS) in a substantial number of non-surgical patients with advanced NET. Our aim was to prospectively determine the efficacy of a combination of radical loco-regional surgery and PRRT in patients with metastasised NET. Methods: A set of inclusion criteria was defined (e.g. G1/G2 NET, initial tumour diagnosis, treatment naïve patient, stage IV NET, positivity on 68Ga DOTA- PET/CT, eligibility for surgery and PRRT). Patients underwent PRRT within 3 months following surgery. Follow-up included biochemistry and imaging. In a sub-cohort, blood-based neuroendocrine gene transcript analysis of 51 genes (NETest) was used to define the effectiveness of treatment. Outcome measures included 5-year overall survival (OS) and PFS from initial diagnosis. Results: Twenty-five patients (5 PNET, 20 SBNET) met eligibility criteria and were included. There were 13 men (52%) and mean age was 57.1 years. All patients with SB NET underwent right hemicolectomy, terminal ileal resection and mesenteric lympadenectomy. In all PNET patients only limited pancreatic resection was required. The median number of PRRT cycles was 4 (range 2-6). Post-treatment mortality was 0%. Surgical morbidity was 12% (all Clavien-Dindo grade 1). Transient grade 1 toxicity occurred post-PRRT in 40%. NETest scores were increased in 8 patients (100%) pre-operatively and decreased in all following treatment. NETest decreases correlated with diminished tumour volume (R2=0.37, p=0.02). Median follow-up was 48 months (range 12-72months). Five-year OS was 90% and 5-year PFS was 84.3%. Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NET. The NETest accurately measures the effectiveness of treatment.

scholarly journals The next generation of peptide receptor radionuclide therapy

2019 ◽  
Vol 26 (8) ◽  
pp. C7-C11 ◽  
Author(s):  
Tessa Brabander ◽  
Julie Nonnekens ◽  
Johannes Hofland
Keyword(s):  
Radionuclide Therapy ◽  
Radiation Effects ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Heat Shock Protein 90 ◽  
Neuroendocrine Neoplasms ◽  
New Developments ◽  
Peptide Receptor ◽  
Promising Target ◽  
New Findings

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-[Tyr3]octreotate has been successfully developed in the last decades for the treatment of neuroendocrine neoplasms. However, different methods to improve the objective response rate and survival are under investigation. This includes changes of the radioligand, dosimetry and combination therapy with different agents, such as radiosensitisers. Hofving et al. recently reported, in the April 2019 issue of Endocrine-Related Cancer, the use of heat-shock protein 90 (Hsp90) modulation to augment radiation effects as a new promising target for radiosensitisation. In this commentary, new developments in the field of PRRT are discussed, placing these new findings about Hsp90 inhibitors into context.

First results for Australasian Gastrointestinal Trials Group (AGITG) control net study: Phase II study of 177Lu-octreotate peptide receptor radionuclide therapy (LuTate PRRT) +/- capecitabine, temozolomide (CAPTEM) for midgut neuroendocrine tumors (mNETs).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 604-604 ◽  
Author(s):  
Nick Pavlakis ◽  
David Turner Ransom ◽  
David Wyld ◽  
Katrin Marie Sjoquist ◽  
Rebecca Asher ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Radionuclide Therapy ◽  
Single Agent ◽  
Tumour Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Phase Iii ◽  
Study Phase ◽  
Peptide Receptor

604 Background: Single agent 177Lu-octreotate peptide receptor radionuclide therapy is now a standard of care for progressive mNETS. High activity was seen with LuTate and concurrent CAPTEM chemotherapy in a single arm Phase I/II trial. This study was undertaken to determine the relative activity of adding CAPTEM to LuTate PRRT in patients with mNETs. Methods: Non-comparative randomised open label phase II trial of PRRT +/- CAPTEM in patients with mNETs, with 2:1 randomisation: PRRT /CAPTEM (experimental arm) vs. PRRT (control). PRRT /CAPTEM: 7.8GBq LuTate day(D) 10, 8 weekly (wkly) x 4, with b.i.d. oral CAP 750mg/m2 D1-14 & TEM 75mg/m2 D10-14, 8 wkly x 4, vs. PRRT 8 wkly x 4. Primary endpoint: progression free survival (PFS) at 15 months assuming 15 month PFS of 66.4% in the control arm, aiming for PFS rate > 80%; secondary endpoints: objective tumour response rate (complete or partial response) (OTRR), clinical benefit rate (complete or partial response, stable disease) (CBR), toxicity, and QOL. Results: 47 patients enrolled (Dec 2015 - Feb 2018): 33 PRRT/CAPTEM and 14 PRRT. Two patients withdrew prior to treatment. Patient characteristics were balanced except gender (female 58% vs. 14%). Two patients received 2 prior systemic regimens. After a median follow-up of 32 months, the 15 month PFS was 90% (95% CI: 73-97%) v 92% (95% CI: 57-99%); OTRR 25% vs 15%; and CBR 97% vs 92% for PRRT/CAPTEM v PRRT respectively. For treatment related adverse events 22/32 CAPTEM patients experienced one Grade 3 event (69%) vs 5/13 (38%, PRRT); 4/32 pts experienced one Grade 4 event (13%) v 1/13 (8%) respectively. Only one patient failed to complete therapy due to toxicity (PRRT/CAPTEM). Conclusions: This initial planned analysis demonstrates similarly high 15 month PFS for CAPTEM/PRRT relative to PRRT alone. OTRR is numerically higher but at the cost of greater toxicity. Longer follow up is required to determine if the activity of PRRT/CAPTEM is sufficient to warrant Phase III evaluation. Clinical trial information: ACTRN12615000909527.

scholarly journals Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy

2019 ◽  
Vol 43 (2) ◽  
pp. 246-253 ◽  
Author(s):  
A. J. A. T. Braat ◽  
H. Ahmadzadehfar ◽  
S. C. Kappadath ◽  
C. L. Stothers ◽  
A. Frilling ◽  
...  
Keyword(s):  
Liver Disease ◽  
Clinical Response ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Entire Study ◽  
Peptide Receptor ◽  
Resin Microspheres

Abstract Purpose Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. Methods Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. Results Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3–4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8–5.1 years] after radioembolization for the entire study population was found. Conclusion Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. Level of Evidence 4, case series.

scholarly journals Achieving objective response in treatment of non-resectable neuroendocrine tumors does not predict longer time to progression compared to achieving stable disease

2020 ◽  
Author(s):  
Espen Thiis-Evensen ◽  
Amalie Christine Poole ◽  
Hong-Thien Thi Nguyen ◽  
Jon Sponheim
Keyword(s):  
Neuroendocrine Tumors ◽  
Stable Disease ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Treatment Modalities ◽  
Time To Progression ◽  
Who Grade ◽  
Peptide Receptor ◽  
Tumor Load

Abstract Background: There are several treatment modalities for unresectable neuroendocrine tumors. Traditionally, the aim of these treatments has been to reduce the tumor load; referred to as objective response (OR). Less emphasis has been put on inducing the tumors to stop growing without a reduction in total tumor load; termed as stable disease (SD). We wanted to investigate whether achieving OR compared to obtaining SD predicted a longer time to progression (TTP) in patients with neuroendocrine tumors (WHO Grade 1 and 2) treated with peptide receptor radionuclide therapy, chemotherapy or molecular targeted therapy. Methods : Patients treated with either peptide receptor radionuclide therapy (PRRT) with 177 Lutetium-DOTA-octreotate, the chemotherapy combination streptozotocin/5-fluorouracil or everolimus were retrospectively assessed to evaluate the effect of the treatments on disease progression. We analyzed the TTP for patients for each treatment modality and compared the TTP between those who achieved OR and those who achieved SD. Results: Altogether 56 patients treated with PRRT, 32 treated with streptozotocin/5-fluorouracil and 52 treated with everolimus were included in the analyses. The median TTP for those treated with PRRT and achieving OR was 31 months, the TTP for those achieving SD was 43 months (p=0,2). For patients treated with streptozotocin/5-fluorouracil the results were: OR: 18 months, SD: 23 months (p=0,9) and for those treated with everolimus; OR: 9 months, SD: 20 months (p=0,5), respectively. We found no differences between patients achieving OR compared to SD regarding age, sex, stage, primary tumor location, Ki-67% or ongoing treatment with somatostatinanalogues. Conclusions: We found no treatment benefit with regard to TTP for our patients that experienced OR compared to those who achieved SD, but a trend toward longer TTP among patients with SD.

Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 623-623
Author(s):  
Heying Duan ◽  
Gaia Ninatti ◽  
Bradley Girod ◽  
Valentina Ferri ◽  
Pamela L. Kunz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Single Institution ◽  
Free Survival ◽  
Peptide Receptor ◽  
Low Toxicity

623 Background: Neuroendocrine tumors (NETs) are rare but increasing in incidence. The only curative treatment is surgery, which in many cases is not an option due to metastatic disease at diagnosis. The NETTER-1 study showed high efficacy and low toxicity of peptide receptor radionuclide therapy (PRRT) for midgut NETs. Here, we present our initial experience with PRRT in the treatment of patients with NET. Methods: Fifty-two patients (27 males and 25 females; 37 - 81 yo, mean ± SD: 61.8 ± 10.6 years) with documented progressive NET (25 pancreas, 17 small intestine, 1 coecum, 4 unknown primary, 3 paragangliomas, and 2 pheochromocytomas) were referred to undergo PRRT at our institution from July 2018 to September 2019. Laboratory tests were obtained at baseline, 1 week before each cycle and every 3 months following treatment. Progression-free survival (PFS), objective response rate (ORR) and toxicity were assessed. An interim overall survival (OS) analysis was performed. Results, when possible, were compared with the NETTER-1 trial. Lines of therapy were documented. Results: 22/52 (42%) patients completed all 4 cycles of PRRT. 18/52 (34%) patients are currently being treated. 12/52 (23%) patients had to discontinue treatment. Hematotoxicity was the only side effect which can be related to PRRT. The 6-month and 9-month PFS rate was 82.4% and 66.8% respectively vs. 89% and 84% in the NETTER-1 trial. The ORR was 36% vs. 18% in the NETTER-1 trial. In the interim OS analysis, 6 deaths occurred. In contrast to the NETTER-1 study, PRRT in our patient cohort was performed later in the course of treatment (median lines of therapy before PRRT = 4 ±1.3 (range 1-6)). Conclusions: Our preliminary data show overall good results of PRRT in patients with NETs. However, compared to the NETTER-1 trial, PFS is shorter which is most likely due to the extensive pretreatment, but ORR was higher. [Table: see text]

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