Eruption of Metastatic Paraganglioma After Successful Therapy with 177Lu/90Y-DOTATOC and 177Lu-DOTATATE

Abstract

Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life. We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on 68 Ga-DOTATATE PET/CT and 111 In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient. Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or 18 F-FDG PET/CT SUV max values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit.

Familial SDHB gene mutation in disseminated non-hypoxia-related malignant paraganglioma treated with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE

“…Similar tumor response rates were noted for 90 Y-and 177 Lu-based agents (12). However, severe adverse reactions following [ 177 Lu]Lu-DOTATATE treatment were also reported in patients with paraganglioma, including catecholamine crisis and tumor lysis syndrome (13), as was marked progression of metastatic paraganglioma following initial partial response to PRRT (14).…”

Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD

“…68 Ga-RGD PET/CT can also be used to evaluate the response to therapy after 177 Lu-EB-RGD treatment; further therapy cycles can be cancelled if there is no or low uptake on posttreatment PET imaging (indicative of a complete or partial response). The principles and expertise required in RGD-based NSCLC theranostics broadly parallel those using 68 Ga/ 177 Lu-labeled DOTATATE for metastatic NETs (26,27) or PSMA for metastatic CRPC (24,28). However, based on previous trials using peptide receptor radionuclide therapy or peptide radioligand therapy, three to four cycles of 177 Lu-DOTATATE/ 177 Lu-PSMA are usually required for an entire treatment paradigm, Targeted Radionuclide Therapy by 177 Lu-EB-RGD…”

“…and each cycle requires a dose of at least 1.85-7.4 GBq of 177 Lu, resulting in a total dosage of 7.4-29.6 GBq 177 Lu (26,(29)(30)(31). Such a huge radiation dosage may result in treatment-related toxic effects on normal organs, such as salivary gland dysfunction, loss of kidney function, and hematological toxicity.…”

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

“…A long-term complication of myelodysplastic syndrome was also observed in an unreported number of PPGL patients receiving the therapy ( 105 ). In a case report by Wolf et al, a dangerous side effect of Lutathera ® in two m PGL patients was hyperprogression of m PGL disease after three cycles of 90 Y/ 177 Lu-DOTATOC (cycle one was 90 Y, and cycle two and three were 177 Lu) in patient A and two cycles of 177 Lu-DOTATATE in patient B ( 107 ). Future reporting of adverse effects of SSA-based PRRT is important in assessing the safety of this therapy in PPGL patients to determine whether the therapy can be effectuated in patients, without life-threatening side effects.…”