Exceptional Response of Rare Plasmacytoid Variant Prostate Cancer Post 177Lu-PSMA Therapy Seen on 68Ga-PSMA PET/CT.

ABSTRACT: Plasmacytoid is a rare variant of acinar prostatic adenocarcinoma. The aggressive type is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies, and an overall poor prognosis. Here we present pretherapy and posttherapy 68Ga-PSMA PET/CT images showing an exceptional response to 177Lu-PSMA therapy. This case demonstrates the usefulness of both 68Ga-PSMA PET/CT in assessing the tumor PSMA avidity and the potential of 177Lu-PSMA therapy in these patients.

The Outcome and Safety of Re-challenge Lutetium-177 PSMA (177Lu-PSMA) Therapy with Low-Dose Docetaxel as a Radiosensitizer-a Promising Combination in Metastatic Castrate-Resistant Prostate Cancer (mCRPC): a Case Report.

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (PSMA-RLT) with lutetium-177 (177Lu-PSMA) has been used in metastatic castrate-resistant prostate cancer (mCRPC), and retrospective data have shown this therapy to be favourably safe with attractive clinical responses. Re-challenge 177Lu-PSMA therapy in early responders has been shown to be safe and effective. We report the use of low-dose Taxol-based chemotherapy (modified dose 25 mg/m2 weekly × 6 weeks) as a radiosensitizer with re-challenge 177Lu-PSMA therapy (4 cycles). In a period of 3 years, the patient underwent a total of 8 cycles of 177Lu-PSMA with a cumulative dose of 51.8 GBq. All therapies were uneventful and well tolerated. There was a good response to re-challenge 177Lu-PSMA therapy and low-dose docetaxel (Taxol-177Lu-PSMA) with no recorded tumour resistance.

The impact of the extent of the bone involvement on overall survival and toxicity in mCRPC patients receiving [177Lu]Lu-PSMA-617: a WARMTH multicentre study.

INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

INTRODUCTION: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. MATERIALS AND METHODS: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. RESULTS: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. CONCLUSION: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.

The association of human immunodeficiency virus and skeletal metastases in breast cancer using Tc-99m methyl diphosphonate bone scan.

Skeletal involvement occurs in 30%-70% of all cancer patients, with breast cancer (BC) being the leading cause for bone metastases in women and prostate cancer in men followed by lung cancer. Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome. It is yet unknown what is the impact of HIV to the onset and progression of bone disease in BC. The purpose of the study was to determine the association of HIV infection and skeletal metastases in BC using skeletal scintigraphy. A retrospective analysis of 25 female BC patients' bone scans was performed. The 25 bone scans of 12 patients known HIV positive and 13 patients who were known HIV negative, of similar age and histology, were compared. All 13 HIV negative patients had a positive bone scan. Of the 12 HIV-positive patients, 4 patients on highly active antiretroviral therapy (HAART) had positive bone scans for skeletal metastases. The remaining eight HIV-positive patients had negative bone scans, of which six were on HAART and two were not on HAART. In our study, HIV infection was not found to be a contributing risk factor for skeletal metastases. From our small series, it appears that HIV patients and on HAART have a delay in the onset of skeletal metastases in BC.

The Complimentary Role of Methoxy-Isobutyl-Isonitrile and Hand-Held Gamma Probe in Adamantinoma.

Adamantinoma is a rare locally aggressive osteolytic tumor that is found 90% of the time in the diaphysis of the tibia with the remaining lesions found in the fibula and long tubular bones. A case of adamantinoma of the tibia is presented. The added value of nuclear medicine investigations in the workup of this patient is described. A three-phase whole body (99m)Tc-methylene diphosphonate bone and a whole body (99m)Tc-methoxy-isobutyl-isonitrile scans were complimentary in the demarcation of viable bone tumor and the assessment of the remainder of the bone and soft tissue to exclude other sites. Intra-operative assistance with a hand-held gamma probe, guided the biopsy of the most metabolically active tumor tissue. Histology revealed a biphasic tumor composed of epithelial and fibrous components, in keeping with an adamantinoma.