Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE

Vyakaranam, Achyut Ram; Crona, Joakim; Norlén, Olov; Granberg, Dan; Garske-Román, Ulrike; Sandström, Mattias; Fröss-Baron, Katarzyna; Thiis‐Evensen, Espen; Hellman, Per; Sundín, Anders

doi:10.3390/cancers11070909

Cited by 62 publications

(56 citation statements)

References 19 publications

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“…177 Lu-tetra-aza-cyclo-dodecanetetraacetic acid–DPhe1-Tyr3-octreotate (DOTATATE) has shown favorable efficacy in controlling symptoms and tumor progression in most of the previous studies ( 5 , 6 ). A recently published meta-analysis has reported good efficacy (disease control rate: 80% (95% CI: 77–89%)) with an encouraging safety profile ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…Identifying predictors of early response to PRRT may help with appropriate patient selection. So far, the only recognized predictor of response to PRRT in PPGL patients is the Ki-67 labeling index ( 6 ). Various studies of PRRT in neuroendocrine tumors (NET) have found baseline SUV max as an important predictor of response to PRRT ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

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177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Jaiswal¹,

Sarathi

Memon³

et al. 2020

Endocrine Connections

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Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/ inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/ inoperable PPGL. Methods: This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (Plasma free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy. Results: A total of 15 patients PCC (4), sPGL (4), HNPGL (5), PCC+sPGL (1), HNPGL+sPGL (1) were included. The median duration of follow up was 27 (range: 11-62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53 %), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis presence of PGL (p= 0.044) and baseline SUVmax >21 (p < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and haematotoxicity. Conclusion: 177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Jaiswal¹,

Sarathi

Memon³

et al. 2020

Endocrine Connections

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“…Coupled with 68 Ga-imaging ( Figure 10 ), it represents a powerful theranostic tool for the management of neuroendocrine tumors (NETs) [ 175 ]. Current research with [ 177 Lu]-DOTATATE aims to improve the safety and efficacy of this procedure, enlarge possible indication, notably in advanced, poorly-differentiated, GEP-NETs, [ 176 , 177 ] or other NETs, such as pheomochromocytoma or paraganglioma [ 178 , 179 ].…”

Section: Targeting Of Somatostatin Receptors With Radiopharmaceutimentioning

confidence: 99%

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

et al. 2020

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Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

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“…In a recently published retrospective study by Vyakaranam et al,22 patients received 177 Lu-DOTATATE (n = 3 with four cycles of 7.4 GBq and n = 19 with dosimetry-guided PRRT where as many cycles (3-11) were administered until 23 Gy to the kidneys or 2 Gy to bone marrow was reached) achieving a median OS of 49.6 (range 8.2-139) months and a median PFS of 21.6 (range 6.7-138) months (Vyakaranam et al 2019). Nine of 22 patients treated were progressive at start.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

“…Endocrine-Related Cancer undergo both 123 I-MIBG and 68 Ga-DOTA-SSA imaging, and based on the results, the first-line therapy should be chosen (Vyakaranam et al 2019). In case of mosaic expression of the two tracers, treatment with both can be considered, and if any lesion/s lack uptake of both the tracers, then it can be targeted by additional beam radiation (Vyakaranam et al 2019). Furthermore, PRRT with combined and/or maintenance cold SSA therapy should be considered as it demonstrated superior results compared to PRRT monotherapy in NETs (Yordanova et al 2018).…”

Section: :11mentioning

confidence: 99%

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

Taïeb

Jha

Treglia

2019

Endocrine-Related Cancer

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In recent years, advancement in genetics has profoundly helped to gain a more comprehensive molecular, pathogenic, and prognostic picture of pheochromocytomas and paragangliomas (PPGLs). Newly discovered molecular targets, particularly those that target cell membranes or signaling pathways have helped move nuclear medicine in the forefront of PPGL precision medicine. This is mainly based on the introduction and increasing experience of various PET radiopharmaceuticals across PPGL genotypes quickly followed by implementation of novel radiotherapies and revised imaging algorithms. Particularly, 68Ga-labeled-SSAs have shown excellent results in the diagnosis and staging of PPGLs and in selecting patients for PRRT as a potential alternative to 123/131I-MIBG theranostics. PRRT using 90Y/177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control. However, more well-designed prospective studies are required to confirm these findings, in order to fully exploit PRRT’s antitumoral properties to obtain the final FDA approval. Such an approval has recently been obtained for high‐specific-activity 131I-MIBG for inoperable/metastatic PPGL. The increasing experience and encouraging preliminary results of these radiotherapeutic approaches in PPGLs now raises an important question of how to further integrate them into PPGL management (e.g. monotherapy or in combination with other systemic therapies), carefully taking into account the PPGLs locations, genotypes, and growth rate. Thus, targeted radionuclide therapy (TRT) should preferably be performed at specialized centers with an experienced interdisciplinary team. Future perspectives include the introduction of dosimetry and biomarkers for therapeutic responses for more individualized treatment plans, α-emitting isotopes, and the combination of TRT with other systemic therapies.

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Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE

Cited by 62 publications

References 19 publications

177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

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