Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study.

PURPOSE: Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [225Ac]Ac-PSMA-617, a targeted alpha therapy (TAT) that administers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. In this study, we report the long-term survival outcomes of this novel therapy in a series of patients with mCRPC who have exhausted all standard treatment options. METHODS: The study enrolled patients with mCRPC who had shown resistance to standard lines of therapies, including next-generation anti-androgen therapies and taxane-based chemotherapies. These eligible patients received treatment with [225Ac]Ac-PSMA-617 at 100-150 kBq/kg doses administered every 8 weeks. The primary objective of the study was to assess overall survival (OS), while secondary objectives included evaluating radiological progression-free survival (rPFS), monitoring serum prostate-specific antigen (PSA) levels as a measure of biochemical response, and assessing adverse events using the CTCAE v5.0 grading system. RESULTS: Among the 63 initially enrolled patients, a total of 56 patients who had completed at least two cycles of [225Ac]Ac-PSMA-617 were included in this study. The mean age was 67 years (range, 39-87) and patients received a total of 204 cycles of [225Ac]Ac-PSMA-617 TAT. 91% of patients exhibited any PSA decline, with 67.8% experiencing a decline of 50% or more. The median follow-up was of 22 months (range: 6-59 months). Imaging-based disease progression was observed in 68% of patients, and 66% of patients succumbed to the disease. The median OS was 15 months (95% CI: 10-19). In univariate analysis, factors such as lack of >50% PSA decline (P=0.031), Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher (P=0.048), and radiological progression (rPD) (P<0.001) were found to be predictors of poor OS. However, in multivariate analysis, only rPD emerged as an independent prognostic factor with a hazard ratio (HR) of 8.264 (95% CI: 1.429-16.497, P=0.004). The estimated median rPFS was 9 months (95% CI: 7-15). Moreover, patients who demonstrated any PSA decline had a median rPFS of 10 months compared to only 3 months in patients without any PSA decline (multivariate HR: 6.749; 95% CI: 1.949-23.370; P=0.002). Fatigue was one of the most common treatment-emergent adverse events, with grades 1/2 occurring in 70% of patients and grades 3 or higher in 3.5% of patients. This fatigue was transient and resolved before the next treatment cycle. Additionally, approximately one-third of patients experienced xerostomia (grades 1/2: 32.1%). CONCLUSION: [225Ac]Ac-PSMA-617 targeted alpha therapy, was found to be well-tolerated with acceptable adverse events and effective in the treatment of patients with end-stage mCRPC.

Late Local and Distant Recurrence of Apparently Benign Paraganglioma.

Paraganglioma-pheochromocytoma (PPGLs) are relatively rare catecholamine-secreting tumors of chromaffin origin. Due to the sympathetic effects of catecholamine excess, their presentation may range from non-specific symptoms to dangerous hypertensive crises. We present the case of a 36-year-old lady with recurrent paraganglioma (PGL) who presented in emergency with hypertensive crisis. She had a history of surgery for left-sided PGL 18 years earlier. Imaging showed local recurrence with pulmonary metastases and blood biochemistry showed raised urinary metanephrines. In view of her poor general condition, we undertook a staged surgical approach for management. She first underwent en-bloc excision of recurrent PGL with left nephrectomy. Nine weeks later, she underwent a pulmonary metastasectomy. This staged surgical approach resulted in the stabilization of blood pressure and normalization of urinary catecholamine. Although most of these tumors are indolent by nature, this case highlights the metastatic potential of apparently benign PGL. This case explores the possibility of a staged surgical approach in a high-risk patient and emphasizes the need for long-term follow-up in these cases.

18F-FDG PET/CT in cyst infection in autosomal dominant polycystic kidney disease.

Infection of a cyst within an autosomal dominant polycystic kidney disease (ADPKD) is a serious complication. Diagnosis with conventional imaging techniques such as ultrasonography, computed tomography (CT), and magnetic resonance imaging can be sometimes challenging. The definite diagnosis is analysis of the cyst fluid, but cyst punctures can cause bleeding, rupture, and contamination of adjacent cysts. Recently, FDG PET/CT has been reported as a sensitive tool for detection of cyst infection. We describe a case of 63-year-old woman with infected cysts in the left kidney, in whom accurate diagnosis was made on FDG PET/CT. FDG PET/CT is an important investigation in patients with fever of uncertain etiology, where renal cyst infection is a possible cause, but other etiologies also need to be ruled out.

SMARCB1 (INI1)-deficient thyroid carcinoma: A novel entity expanding the spectrum of tumors with INI1 loss.

BACKGROUND: Biallelic loss of SMARCB1/INI1 is associated with highly aggressive malignancies, namely renal and extra-renal malignant rhabdoid tumors, and atypical teratoid/ rhabdoid tumor. Increasing availability of molecular testing and immunohistochemical stains acting as surrogate tools to genetic analysis has led to an increasing recognition of SMARCB1 loss in a variety of neoplasms. Interestingly, many of these lack the typical rhabdoid features ascribed to this group of tumors, making their identification difficult. CASE PRESENTATION: We describe the cytological, histological, immunohistochemical and molecular features of the first case of primary SMARCB1 (INI1)-deficient carcinoma of the thyroid gland in literature. The tumor was unique in various aspects; apart from never having been documented at this location, it showed extensive glandular differentiation, mimicking metastatic adenocarcinoma. CONCLUSION: Awareness of this novel entity is essential to avoid misdiagnosis, and for appropriate management, especially in an era of increased feasibility of targeted therapy.

Assessment of the role of early dynamic PET/CT with 18F-fluorocholine in detection of parathyroid lesions in patients with primary hyperparathyroidism.

OBJECTIVE: The aim of the present study was to assess the utility of early dynamic PET/computed tomography with fluorine-18-fluorocholine (F-FCH) in detecting parathyroid lesions and in differentiating parathyroid lesions from cervical lymph nodes (LNs). PATIENTS AND METHODS: A prospective study was conducted on 14 patients with clinical and biochemical evidence of primary hyperparathyroidism by having a positive Tc-sestaMIBI scan. Patients underwent early dynamic F-FCH PET/computed tomography scan, after the administration of 5-8 mCi (185-296 MBq) at 1 min per frame for 15 min. Delayed static images of 2-3 min per bed position were taken between 45 and 60 min. 3D-VOI's were plotted on parathyroid adenoma, cervical LN and thyroid. Dynamic and static images were interpreted by two expert nuclear medicine physicians independently and the following parameters were calculated for parathyroid adenoma and cervical LN: maximum standardized uptake value (SUVmax), time activity curve for SUVmax, t-peak. Adenoma to thyroid ratio (A/T) and cervical LN to thyroid ratio were calculated for each dynamic and static image. RESULTS: Fourteen (eight females and six males) patients were included in the study. All patients showed a higher SUVmax in the adenoma and the cervical LN in the early dynamic images as compared with delayed static images. A/T ratio obtained in the dynamic and static images were compared and found to have insignificant difference (P=0.2255). The difference between mean A/T and LN to thyroid ratio was found to be significant (P=0.0117) during the dynamic study. CONCLUSION: A possible explanation of higher SUVmax in the dynamic images in adenomas may be due to the increased vascularity/early F-FCH uptake. Results indicate early dynamic imaging could suffice, without the need for a delayed image after 45 min, and this technique could adequately differentiate a parathyroid adenoma from a cervical LN.

Fluorocholine PET Imaging of Parathyroid Disease.

To give an overview of the potential clinical utility of 18F-fluorocholine PET/CT (FCH PET/CT) in imaging of parathyroid adenoma. Available studies have provided preliminary results of 18F-FCH PET/CT in primary and secondary hyperparathyroidism. Results of various studies have shown that 18F-FCH is a promising upcoming tracer for the detection of parathyroid adenomas, especially when multiple, or having low size. FCH PET/CT has the potential to be a standard investigation in the detection of parathyroid lesions.

Somatostatin Receptor PET/CT Features of Carcinoid Heart Disease.

We present the case of a 35-year-old woman with metastatic neuroendocrine tumor undergoing treatment with long-acting octreotide and Lu-DOTATATE therapy. We present features of carcinoid heart disease on Ga-DOTANOC PET/CT, which revealed dilated right atrium, pericardial effusion, ascites, and congestive hepatopathy apart from the metastatic lesions in the liver. The scan cardiac findings were confirmed by echocardiography. This highlights the significance of identifying such patients early because additional management is required for carcinoid heart disease per se and a cautious approach is needed in administering amino acid infusion during PRRT that can result in fluid overload.

Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study.

PURPOSE: The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. METHODS: One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. RESULTS: There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/µL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. CONCLUSIONS: Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

Comparison of 18F-Fluorocholine Positron Emission Tomography/Computed Tomography and Four-dimensional Computed Tomography in the Preoperative Localization of Parathyroid Adenomas-initial Results.

OBJECTIVE: We aimed to compare the diagnostic accuracy of 18F-Fluorocholine (FCH)-positron emission tomography/computed tomography (PET/CT) and four-dimensional (4D)- CT in detection and localization of eutopic and ectopic parathyroid adenoma (PA) in patients with hyperparathyroidism. MATERIALS AND METHODS: Five patients with primary hyperparathyroidism underwent FCH-PET/CT after 60 min of 185 MBq of intravenous 18F-FCH administration. Images were acquired from head to mediastinum at 3 min per bed position. No intravenous contrast was used. All patients underwent 4D-CT within 2 weeks of the FCH-PET/CT, with a precontrast, post contrast arterial, and venous phase with 75 ml intravenous Iohexol 350 followed by 25 ml saline chase. Histopathology was considered as the gold standard. RESULTS: Both modalities showed 100% concordance in the detection of parathyroid lesions. Both FCH-PET/CT and 4D-CT detected 7 lesions in 5 patients, with 4 patients having a single lesion, and 1 patient having three lesions. Of the 7 reported lesions, 4 were eutopic and 3 were ectopic. No additional lesions were detected by either modality in comparison to the other. All 7 specimens were resected and histopathology showed PA/hyperplasia. CONCLUSION: FCH-PET/CT and 4D-CT are equally efficacious in detection and localization of eutopic and ectopic PA. This may open up the possibility of using FCH-PET/CT in patients with negative conventional imaging who cannot undergo contrast studies.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC.

Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients. MATERIALS AND METHODS: After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software. RESULTS: A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0.003 mGy/MBq. CONCLUSION: Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.

Parathyroid carcinoma with contralateral subcutaneous and breast recurrences: A rare presentation.

BACKGROUND: Parathyroid carcinoma is extremely rare. Correct preoperative and even histopathological diagnosis may be difficult owing to the deceptively bland cytoarchitectural features, especially when presenting with localized disease. Recurrence/metastases developing years later then make the malignant nature obvious. METHODS AND RESULTS: We present here an unusual case of a 32-year-old patient with carcinoma of the left upper parathyroid gland, initially diagnosed as parathyroid adenoma, treated with endoscopic left parathyroidectomy, and later developing subcutaneous metastatic nodules over the medial end of the right clavicle and right anterior chest wall, followed by a right breast deposit. The recurrences, especially subcutaneous ones, were probably secondary to tumor seeding along the track of insertion of the endoscope. CONCLUSION: Involvement of subcutaneous tissue and the breast in parathyroid carcinoma is extremely rare. The case is being reported for its uniqueness along with a discussion of possible appropriate course of management, which may have averted the aggressive clinical course of the disease.

Hemimegalencephaly: A rare cause of hemihypoperfusion on 99m technetium-ethyl cysteinate dimer brain perfusion single-photon emission computed tomography.

Hemimegalencephaly is a rare congenital neuronal migration disorder that can presents with the equally rare finding of hemihypoperfusion on brain perfusion single-photon emission computed tomography (SPECT). It is an extremely rare cause of intractable epilepsy. Technetium-99m ethyl cysteinate dimer (ECD) brain perfusion SPECT is useful in excluding other foci of hypoperfusion in the contralateral since hemispherectomy has been suggested to be the treatment of choice. Furthermore, hemimegalencephaly may present with hyper as well as hypoperfusion on ECD SPECT. We present the case of an 11-year-old male child with intractable seizures who showed hemihypoperfusion in the hemimegalecephalic hemisphere.

Incidental detection of hyperfunctioning thyroid cancer metastases in patients presenting with thyrotoxicosis.

Thyrotoxicosis due to functioning metastases from thyroid cancer is rare. It also presents a therapeutic challenge, as both the metastatic cancer and thyrotoxicosis need to be treated. We present here two cases of thyrotoxicosis which on a routine (99m)Tc-pertechnetate thyroid scan showed extrathyroidal foci of uptake. Two patients who initially presented with thyrotoxicosis underwent a routine thyroid scan. Abnormal uptake in the shoulder was incidentally noted, which prompted us to do a whole body pertechnetate scan in the same sitting, which revealed extensive hyperfunctioning metastases in the lungs and bones. We also discuss the 'Flip Flop' phenomenon in thyroid cancer, which was seen in our case. This report emphasizes the importance of evaluating the abnormal foci of uptake seen on a routine thyroid scan.

Diagnosis of Men-I Syndrome on (68)Ga-DOTANOC PET-CT and Role of Peptide Receptor Radionuclide Therapy With (177)Lu-DOTATATE.

MEN-I is a rare genetic disorder classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary gland, and pancreatic islet cells. We present a case of MEN-I syndrome diagnosed using predominantly nuclear medicine imaging followed by radionuclide therapy, thus emphasizing the role of nuclear imaging in diagnosing and treating MEN-I.

Association of non-traumatic complex regional pain syndrome with adenocarcinoma lung on 99mTc-MDP bone scan.

Complex regional pain syndrome (CRPS) is usually associated with trauma. Rarely, it may be seen in association with malignancies. We present here the bone scan and X-ray findings in the case of a 56-year-male-patient with adenocarcinoma lung who also had non-traumatic CRPS without involvement of the stellate ganglion. The case highlights the fact that spontaneous development of reflex sympathetic dystrophy may be associated with a neoplastic etiology.