Tumor Contrast-Enhancement for Monitoring of PRRT 177Lu-DOTATATE in Pancreatic Neuroendocrine Tumor Patients

Pettersson, Olof; Fröss-Baron, Katarzyna; Crona, Joakim; Sundín, Anders

doi:10.3389/fonc.2020.00193

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…After completion of PRRT, the tumor vascularization decreased in the majority of P-NET lesions, as reflected by their CT contrast-enhancement. A corresponding reduction in P-NEN vascularization between the CT at baseline and on follow-up CT post-PRRT has previously been reported by Pettersson et al [20]. Thus, although the total administered activity (GBq) was similar in P-NEN and SI-NEN patients, the decline in absorbed doses (Gy) in the tumors over consecutive PRRT cycles was significant in the majority of P-NEN patients, as shown in Figures 3 and 4.…”

Section: Discussionsupporting

confidence: 79%

“…The vascularity of primary pancreatic tumors and P-NENs has earlier been analyzed and was found to correlate to tumor classification and survival [ 18 , 19 ]. Also, fold changes of contrast-enhancement in P-NEN metastases has been shown to correlate to PRRT outcome [ 20 ]. These findings are in agreement with preclinical studies on vascularization in radiated tumors in mice [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

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Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Jahn

Ilan

Sandström

et al. 2021

Cancers

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Dosimetry during peptide receptor radionuclide therapy (PRRT) has mainly focused on normal organs and less on the tumors. The absorbed dose in one target tumor per patient and several response related factors were assessed in 23 pancreatic neuroendocrine neoplasms (P-NENs) and 25 small-intestinal NEN (SI-NENs) during PRRT with 177Lu-DOTATATE. The total administered activity per patient was (mean ± standard error of mean (SEM) 31.8 ± 1.9 GBq for P-NENs and 36 ± 1.94 GBq for SI-NENs. The absorbed tumor dose was 143.5 ± 2 Gy in P-NENs, 168.2 ± 2 Gy in SI-NENs. For both NEN types, a dose–response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in P-NENs. A significant drop in the absorbed dose per cycle was shown during the course of PRRT. Tumor vascularization was higher in P-NENs than in SI-NENs at baseline but equal post-PRRT. The time to progression (RECIST 1.1) was similar for patients with P-NEN (mean ± SEM 30 ± 1 months) and SI-NEN (33 ± 1 months). In conclusion, a dose response relationship was established for both P-NENs and SI-NENs and a significant drop in the absorbed dose per cycle was shown during the course of PRRT, which warrants further investigation to understand the factors impacting PRRT to improve personalized treatment protocol design.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Jahn

Ilan

Sandström

et al. 2021

Cancers

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“…Change in arterial tumor attenuation and contrast enhancement is another criterion, which was recently evaluated by Pettersson et al [ 87 ] in a retrospective cohort of 52 patients with metastatic pNETs who underwent ceCT at baseline, mid-treatment and at 3 months follow-up. Their study showed a significant decrease of the maximum arterial attenuation of liver metastases between baseline (217 ± 62 HU) and follow-up (198 ± 62 HU; p = 0.025).…”

Section: Methodsmentioning

confidence: 99%

The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future

et al. 2020

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The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owed to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

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“…Patients were screened for inclusion using a previously described cohort of PanNET patients (n=151) undergoing PRRT with 177 Lu-DOTATATE (21). Inclusion criteria were at least one hypervascular liver metastasis at baseline on contrast-enhanced computed tomography (CECT) of adequate technical quality.…”

Section: Patients and Imagingmentioning

confidence: 99%

Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE

Pettersson

Fröss-Baron

Crona

et al. 2021

Endocrine Connections

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Background: Monitoring of pancreatic neuroendocrine tumors (PanNET) undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE depends on changes in tumor size, which often occur late. Tumor growth rate (TGR) allows for quantitative assessment of the tumor kinetics expressed %/month. We explored how TGR changes before and during/after PRRT and evaluated TGR as a biomarker for progression-free survival (PFS). Methods: In PanNET patients undergoing PRRT with 177Lu-DOTATATE from 2006 to 2018, contrast-enhanced computed tomography or magnetic resonance imaging was performed before and during therapy. Patients with at least one hypervascular liver metastasis were included. TGR was calculated for the period preceding treatment and for two intervals during/after PRRT. Cox regression was used for the survival analysis. Results: Sixty-seven patients (43 men, 24 women), median age 60 years (range 29-77), median Ki-67 10% (range 1-30) were included. TGR before baseline (n=57) (TGR0) was mean (standard deviation, SD) 6.0 %/month (SD=8.7). TGR at 4.5 months (n=56) (TGR4) from baseline was -3.4 (SD=4.2) %/month. TGR at 9.9 months (n=57) (TGR10) from baseline was -3.0 (SD=2.9) %/month. TGR4 and TGR10 were lower than TGR0 (TGR4 versus TGR0 p=1.63*10-13 and TGR10 versus TGR0 p=9.41*10-15). In the survival analysis, patients with TGR10 ≥0.5 %/month (versus <0.5 %/month) had shorter PFS (median = 16.0 months vs 31.5 months, Hazard Ratio 2.82; 95% Confidence Interval 1.05-7.57, p=0.040). Discussion: TGR in PanNET patients decreases considerably during PRRT with 177Lu-DOTATATE. TGR may be useful as a biomarker to identify the patients with the shortest PFS.

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Tumor Contrast-Enhancement for Monitoring of PRRT 177Lu-DOTATATE in Pancreatic Neuroendocrine Tumor Patients

Abstract: Conclusions: Early changes in contrast-enhancement and arterial attenuation in PNET liver metastases may for CECT monitoring of PRRT yield complementary information to evaluation by RECIST 1.1.

Cited by 8 publications

References 38 publications

Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE; Differences in Tumor Dosimetry, Vascularity and Lesion Metrics in Pancreatic and Small Intestinal Neuroendocrine Neoplasms

The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future

Tumor growth rate in pancreatic neuroendocrine tumor patients undergoing PRRT with 177Lu-DOTATATE

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