Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted ¹⁷⁷Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

Abstract

This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTA-TATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptorbased imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and 18 F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. Merkel cell carcinoma (MCC) is an aggressive dermatologic malignancy of the Merkel cells, which are situated just beneath the epidermis and close to nerve endings that receive the touch sensation. Known risk factors for the development of MCC are exposure to the sun, a weak immune system, and psoralen and ultraviolet A therapy for psoriasis (1). Because Merkel cells are thought to have a neuroendocrine origin and function, MCC is also referred to by the synonyms primary neuroendocrine carcinoma of the skin, cutaneous apudoma, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin (1). Although patients who have small tumors without regional spread have a good prognosis after conventional treatment with radiation and chemotherapy (5-y survival, ;80%), those with regional spread have a 5-y survival of only 50% and survival for all stages combined is 60% (2,3). Thus, new therapeutic options for metastatic MCC are needed to improve survival.Examination with both light and electron microscopy and with immunohistochemistry are the primary means of definitively diagnosing the condition. Wide local excision with adjuvant irradiation is the usual treatment approach, with neck dissection added if there are clinically positive nodes. Contrastenhanced CT has traditionally been the standard modality for staging, but the potential of 18 F-FDG PET and somatostatin receptor-based 68 Ga-DOTANOC/TATE PET/CT for staging has also been described (4,5). In an early report (4), metastatic disease in subcentimeter-sized lymph nodes was seen on pretreatment 18 F-FDG PET/CT but not on CT, and posttreatment 18 F-FDG PET correctly depicted a response to therapy. In a more recent report (5), on 24 MCC patients imaged with 68 Ga...

18F-FDG and 68Ga-somatostatin analogs PET/CT in patients with Merkel cell carcinoma: a comparison study

“…We found that 18 F-FDG and 68 Ga-somatostatin analogs provide good and equivalent diagnostic performance, with no significant differences either on a patient-based analysis or on a lesion-based analysis. From literature data, only few MCC patients have been imaged using both PET tracers, with better or equivalent performance of 68 Ga-SRI compared to 18 F-FDG PET/CT [ 25 – 27 ]; however, they are all case reports and, therefore, not reliably comparable with our findings. Similarly, our findings are not comparable with those reported by Lu et al [ 33 ] in the largest series of nine MCC patients who were investigated comparing 18 F-FDG PET/CT to 111 In-pentetreotide SRS.…”

“…Therefore, as shown by our data and reported in the NCCN guidelines [ 17 ], we retain that, in clinical practice, 18 F-FDG PET/CT should not be replaced by 68 Ga-SRI, which should be performed in addition, if clinically indicated. Anyway, it is important to consider that the decision on which tracer to employ at first line should be strongly influenced by the information that is considered more relevant for clinical management, in the perspective of “personalized medicine.” In this regard, 18 F-FDG PET/CT may also add prognostic information, as recently suggested [ 11 , 41 ], while 68 Ga-SRI PET/CT may be useful for both therapy planning and response assessment in a “theranostic strategy” when peptide receptor radionuclide therapy (PRRT) is considered as a further potential treatment option [ 24 , 25 , 27 , 35 , 42 ]. Moreover, with the advent of immunotherapy with immune checkpoint inhibitors, PET/CT imaging with the two different tracers may turn out to play a role in a tailored-treatment approach providing useful and complementary information also in the setting of response assessment and follow-up for advanced MCC [ 43 , 44 ].…”

“…Recent evidences regarding the use of somatostatin analogs labeled with positron emitters ( 68 Ga-peptides) for PET imaging in MCC have shown positive results, suggesting a possible impact on MCC management [ 21 – 24 ]. A direct comparison between 18 F-FDG and 68 Ga-somatostatin receptor imaging ( 68 Ga-SRI) PET/CT in the same MCC patient has been only reported in a few case reports [ 25 – 27 ]. In this regard, potential interesting insights into tumor biology could derive from a head-to-head comparison of both tracers, besides possible implications also in the perspective of a personalized patient management.…”

Molecular and immune targets for Merkel cell carcinoma therapy and prevention

“…In coordination with CT results, these findings provide opportunities for targeted radiotherapy to metastases . Therapeutic radioisotopes, such as the use of peptide receptor radionuclides as internal radiation therapy, have potential in MCC . Trials investigating radionuclides and peptide conjugated receptor analog delivery to neuroendocrine tumors for imaging and therapeutic purposes are ongoing.…”

A rare case of Merkel cell carcinoma presenting as a giant intra-thoracic mass

“…[ 21 ] Furthermore, the metastatic lesions of MCC demonstrated avidity to both somatostatin receptors and (18)F-FDG, and an excellent partial response to a single cycle of peptide receptor radionuclide therapy with (177)Lu-DOTATATE is demonstrated, which may be reasonable as the first-line therapy for metastatic MCC. [ 22 ] The specific biomarkers of MCC include platelet-derived growth factor receptor, CD117, phosphoinositide 3-kinase, PD-L1, p63, vascular endothelial growth factor receptor, Ki-67, CD34, epithelial cellular adhesion molecule (Ep-CAM), nuclear factor kappa B, sonic hedgehog pathway proteins, and matrix metalloproteinase, which have been suggested to predict the prognosis of these patients. [ 2 ] Up to date, no effective systemic treatment for end stage MCC is available.…”