Clinical efficacy of 177Lu‑DOTATATE peptide receptor radionuclide therapy in thyroglobulin‑elevated negative iodine scintigraphy: A “not‑so‑promising” result compared to GEP-NETs
Basu, S.; Parghane, R. V.; Naik, C.
World J Nucl Med 2020; 19: 205-10.
Background:
Lu-177 DOTATATE is a radiolabelled somatostatin analogue which is becoming widely approved for use in the treatment of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) which express somatostatin receptors (SSTR). It has shown considerable efficacy in this regard, and it has been hypothesized that it may also be beneficial in de-differentiated thyroid carcinomas with significant DOTATATE-avid disease.
Purpose:
The authors seek to assess the effect of Lu-177 DOTATATE in treatment of thyroid carcinomas which are associated with elevated thyroglobulin levels and negative iodine scintigraphy (thyroglobulin-elevated negative iodine scintigraphy, TENIS).
Methods:
A retrospective chart review of patients who had undergone Lu-177 DOTATE for metastatic TENIS was undertaken. All patients had initial imaging completed to determine SSTR positivity, for example with Ga-68 DOTATATE which was found to be positive, and had at least one cycle of Lu-177 DOTATATE therapy. There were no exclusion criteria.
Lesions were characterized based on qualitative radiotracer uptake in the initial imaging scan, and patients were categorized based on no uptake (Grade 0), uptake less than the liver (Grade I), uptake equal to the liver (Grade II), and uptake greater than the liver (Grade III). Information collected included patient demographics, metastatic burden, characteristics of the Lu-177 DOTATE treatment, clinical response, and presence of significant hematological or renal toxicity. Clinical response to treatment was assessed as “complete response” (CR), “partial response” (PR), “stable disease” (SD), or “progressive disease” (PD) in each of symptoms, serum thyroglobulin (TG) level, and PET/CT imaging via the PET Response Evaluation Criteria in Solid Tumors (PERCIST). CR was defined as disappearance of symptoms or >75% reduction in TG; PR was 30-75% reduction in symptoms or 30-75% reduction in TG; SD was <30% symptom reduction or <30% change in TG; PD was considered >30% increase in symptoms or new symptoms or >30% increase in TG.
Results:
Eight patients were included: three completed one cycle of Lu-177 DOTATE therapy, two completed two cycles, one completed three cycles, and two completed four cycles. Malignancies included four cases of papillary carcinoma, two follicular variants of papillary carcinoma, one poorly differentiated carcinoma, and one follicular carcinoma; all had metastases. Most patients (6) had Grade II uptake on initial SSTR imaging. None had evidence of significant hematological or renal toxicity.
Four patients exhibited PD with respect to symptoms; three had PR in symptoms, and one had CR of symptoms. Five patients had increased TG (PD); three had reduction in TG (PR). Six patients had PD and two had SD by imaging after 7-16 months without progression.
Discussion:
The literature which exists on the efficacy of SSTR therapy for TENIS is limited: Budiawan et al. found that 2/16 patients had PR, 4/16 had SD, and 5/16 had PD; Versari et al. found 2/11 had PR, 5/11 had SD and 4/11 had PD; finally, Czepczy Nski et al. found 1/6 with PR by imaging and TG, 2/6 with SD by imaging and 4/6 with SD by TG, and 3/6 with PD by imaging and 1/6 with PD by TG. This current work shows similar results.
The authors propose that this relatively poor response of TENIS to SSTR therapy may arise from the lower degree of expression of SSTR in TENIS compared to GEP-NETs, and that TENIS is often FDG-avid implying more aggressive disease.
Conclusion:
Ultimately, the efficacy of SSTR treatment for TENIS has not been shown to be as beneficial as it is for GEP-NETs, but it may have slight benefit in few patients.
Clinical Impact of PET Imaging in Patients With Metastatic Prostate Cancer
Tuncel, M.; Tuncalt, M. C.; Telli, T.; Erman, M.
Clin Nucl Med 2020; 45: 757-64.
Background:
While non-metastatic prostate cancer had high survival rates up to 98.9%, survival rates for metastatic prostate cancer drop to 30%. Knowledge of Imaging features of the disease helps determine prognosis and potential benefits of specific treatments: molecular imaging is growing in importance in metastatic prostate cancer for this reason.
Discussion:
Staging —
PSMA is overexpressed in >90% of prostate cancers, and is more expressed in higher grade cancers. Ga-68 PSMA PET/CT imaging is therefore recommended biochemical recurrence (PSA > 0.2 mg/mL) as it is more sensitive than conventional imaging like bone scintigraphy, CT, or MRI. In a study by McCarthy et al., of 199 patients with no disease on conventional imaging, 74% were found to have PSMA-avid lesions on PET/CT; of 39 who had evidence of oligometastatic disease on conventional imaging, 41% of these were upstaged to polymetastatic. The authors present a case in which Ga-68 PSMA PET/CT elucidated lymph node metastases in a patient whose bone scan revealed a single bone metastasis, in the context of a normal CT scan: this information allowed treatment of all metastases with image-guided stereotactic body radiotherapy. In another case, additional information regarding provided by PET/CT metastatic lymph nodes excluded a patient from the SPARTAN apalutamide clinical trial
The remaining small proportion of prostate cancers (<10%) to not overexpress PSMA, making PSMA PET/CT a poor imaging choice for monitoring these usually poorly differentiated cancers. FDG PET/CT remains of use in these cancers: higher FDG-avidity corresponds with a higher aggressivity of the tumor, implying a poorer prognosis. A number of cases are presented illustrating the value of FDG PET/CT in PSMA-negative prostate cancer, to help guide subsequent treatment decisions.
Treatment —
In highly PSMA-avid lesions, radionuclide therapy becomes a treatment option: beta-emitting Lu-177 PSMA can be invoked in metastatic castration-resistant prostate cancer as a third-line treatment. While it has been shown to result in a reduction in PSA and objective remission, a Phase 3 clinical trial is now underway (Vision). The authors report a case of a 76-year-old man who experienced recurrences following ADT, Docetaxel, Abiraterone, and Cabazitaxel; he was subsequently imaged with Ga-68 PSMA PET/CT, found to have PSMA-avid disease, and treated with Lu-177 PSMA therapy, resulting in disease regression by imaging and PSA levels. Another patient at the authors’ institution did not have such a result, and actually experienced progression, demonstrated by imaging and PSA levels, in the context of disease which was both PSMA- and FDG-avid; he went on to have Ra-223 therapy which he initially deferred due to cost.
Conclusion:
The authors present a pictorial essay outlining the role of PSMA- and FDG-PET in prostate cancer staging and treatment, including representative cases from their centre.
An overview on prostate‑specific membrane antigen uptake in malignancies other than prostate cancer: A pictorial essay
Jafari, E.; Ahmadzadehfar, H.; Dadgar, H.; Assadi, M.
World J Nucl Med 2020; 19:260-5.
Background:
PSMA (prostate-specific membrane antigen) imaging is a technique used to detect the spread of prostate cancer. Conceptually, the radiopharmaceutical localises to prostate cells, which overexpress the PSMA glycoprotein, especially in the case of more advanced cancer; its uptake is localized by the detection of gamma radiation from the radioisotope, often Ga-68 in the case of PSMA PET-CT.
Findings:
Recent research has found that localization of the PSMA radiopharmaceutical is not specific to prostate cancer, but is expressed in other cancers as well due to neovascularization. The authors summarize some of these case reports which illustrate PSMA uptake in malignancies later pathologically identified as brain, thyroid, breast, lung, hepatic, gynecological, and colorectal cancers. They provide images of PSMA-avid esophageal cancer, cholangiocarcinoma, and pancreatic cancer which are not previously described.
Conclusions:
PSMA imaging, be it planar scintigraphy or PET-CT, is a sensitive means to stage prostate cancer, but interpretation requires awareness of the limits of its specificity which arise from the expression of the PMSA glycoprotein in tumor neovascularization.
References