Myelodysplastic Syndrome Related to Successful Treatment With177Lu-PSMA for Metastatic Castration-Refractory Prostate Cancer.

ABSTRACT: 177Lu-vipivotide tetraxetan (177Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages. Secondary myeloid neoplasm following exposure to DNA-damaging therapy (therapy-related myelodysplastic syndrome [MDS]) is a rare severe complication of 177Lu-oxodotreotide. We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.

The cholesterol-derived metabolite dendrogenin A functionally reprograms breast adenocarcinoma and undifferentiated thyroid cancer cells.

Dendrogenin A (DDA) is a tumor suppressor mammalian cholesterol-derived metabolite and a new class of ligand of the Liver X receptor (LXR), which displays tumor cell differentiation. In human MCF7 breast adenocarcinoma cells, DDA-induced cell differentiation was associated with an increased accumulation of neutral lipids and proteins found in milk indicating that DDA re-activates some functions of lactating cells. Active iodide transport occurs in the normal lactating mammary cells through the sodium/iodide symporter (NIS) and iodide (I) is secreted into milk to be used by the nursing newborn for thyroid hormones biosynthesis. In the present study, we assessed whether DDA may induce other characteristic of lactating cells such as NIS expression and iodine uptake in MCF7 breast cancer cells and extended this study to the papillary B-CPAP and undifferentiated anaplastic 8505c thyroid cancer cells. Moreover, we evaluated DDA impact on the expression of thyroid specific proteins involved in thyroid hormone biogenesis. We report here that DDA induces NIS expression in MCF7 cells and significantly increases the uptake of 131-I by acting through the LXR. In addition, DDA induces phenotypic, molecular and functional characteristics of redifferentiation in the two human thyroid carcinoma cell lines and the uptake of 131-I in the undifferentiated 8505c cells was associated with a strong expression of all the specific proteins involved in thyroid hormone biosynthesis, TSH receptor, thyroperoxidase and thyroglobulin. 131-I incorporation in the 8505c cells was stimulated by DDA as well as by the synthetic LXR ligand, GW3965. Together these data show that the re-differentiation of breast and thyroid cancer cells by DDA, is associated with the recovery of functional NIS expression and involves an LXR-dependent mechanism. These results open new avenues of research for the diagnosis of thyroid cancers as well as the development of new therapeutic approaches for radioiodine refractory thyroid cancers.

Diagnostic and Therapeutic Uptake of Intrathyroid Metastasis of Midgut Neuroendocrine Tumor on 68Ga-DOTANOC PET/CT and 177Lu-DOTATATE Imaging.

A 58-year-old woman with 5-year history of grade 1 progressive metastatic intestinal neuroendocrine tumor with metachronous liver metastases initially treated by surgery and liver embolization underwent Ga-DOTANOC PET/CT before Lu-DOTATATE therapy. Ga-DOTANOC PET/CT revealed increased uptake in several liver metastases and right iliac lymph nodes, consistent with radiopeptide therapy, including a hypodense isthmic thyroid nodule. Fine needle ultrasound-guided biopsy of the thyroid nodule was realized. Immunohistochemistry was positive for CD56, chromogranin, and synaptophysin and negative for calcitonin, confirming neuroendocrine tumor intrathyroid metastasis. Lu-DOTATATE SPECT/CT showed therapeutic uptake on the thyroid metastasis.

Incidental Finding of Intrathyroid Metastases of Prostatic Cancer on 18F-Choline PET/CT.

An 85-year-old man with a 2-year history of prostate cancer, treated with radiotherapy and hormonal therapy, presented increased prostatic-specific antigen levels. F-choline PET/CT showed focal prostatic uptake consistent with known local recurrence, increased uptake of 2 hypodense thyroid nodules and of 2 left cervical lymph nodes, suspected as thyroid cancer. Neck ultrasound confirmed the high risk of malignancy, and a guided biopsy (of a thyroid nodule and cervical lymph node) revealed cellular infiltrates thyroid transcription factor-1 (TTF-1) negative and prostatic-specific antigen positive, confirming intrathyroid and cervical lymph node metastases of prostate cancer. PET/CT changed the disease staging. Chemotherapy was initiated.

Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases: a pilot study.

PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. RESULTS: MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. CONCLUSION: Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for patient selection and treatment optimization.

Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response.

Radioiodine is a therapeutic option in Europe for Graves' disease (GD) and toxic multinodular goiter (MNG). PURPOSE: To compare empiric and calculated I activities using 2013 EANM recommendations. To look for predictive factors of therapeutic response to an empiric activity of I. To assess clinical situations favoring calculated treatment modalities. PATIENTS AND METHODS: Prospective monocentric study of clinical outcomes at 1 year follow-up in 86 patients with GD and MNG who received empiric I therapeutic activities (348-939 MBq). Differences between empiric and calculated activities were confronted to clinical outcomes. Physicians were not aware of the calculated activity at the time of prescription. RESULTS: One year after treatment, 9% (5/57) of GD patients and 7% (2/29) of MNG patients were still in a hyperthyroid state. Thyroid volume was reduced by 67% for GD and by 50% for MNG. In GD, empiric I activities were higher than calculated ones (564±131 vs. 316±319 MBq, P<0.001) in 93% (53/57) of patients. Pretherapeutic thyroid volume (>26 ml for GD; >40 ml for MNG) was associated with persistent hyperthyroidism. CONCLUSION: Empirically administered I for GD and MNG was associated with very high efficacy in thyroid function control and no side effects. Thyroid volume reduction did not preclude treatment efficacy. Activity calculation could be a useful method for treating patients with GD and thyroid volumes higher than 26 ml or patients with MNG and thyroid volumes higher than 40 ml. A selective approach based on pretherapeutic thyroid volume and radioiodine biokinetics might improve treatment success.