3-Year Freedom from Progression After 68Ga-PSMA PET/CT-Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial.

68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in men with biochemical recurrence (BCR) after radical prostatectomy (RP), but its longer-term prognostic or predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for a 3-y freedom from progression (FFP) in men with BCR after RP undergoing salvage radiotherapy (sRT). Methods: This prospective multicenter study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA PET with a rising level of prostate-specific antigen (PSA) after RP. Management after PSMA PET was recorded but not mandated. PSMA PET protocols were standardized across sites and reported prospectively. Clinical, pathologic, and surgical information; sRT; timing and duration of androgen deprivation; 3-y PSA results; and clinical events were documented. FFP was defined as a PSA rise of no more than 0.2 ng/mL above nadir after sRT, with no additional treatment. Results: The median PSA was 0.26 ng/mL (interquartile range, 0.15-0.59 ng/mL), and follow-up was 38 mo (interquartile range, 31-43 mo). PSMA PET had negative results in 34.6% (90/260), showed disease confined to the prostatic fossa in 21.5% (56/260), showed disease in the pelvic nodes in 26.2% (68/260), and showed distant disease in 17.7% (46/260). Of the patients, 71.5% (186/260) received sRT: 38.2% (71/186) to the fossa only, 49.4% (92/186) to the fossa plus the pelvic nodes, and 12.4% (23/186) to the nodes alone or stereotactic body radiation therapy. PSMA PET was highly predictive of FFP at 3 y after sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative results or fossa-confined findings versus 45% (39/86) with extrafossa disease (P < 0.0001). On logistic regression, PSMA PET was more independently predictive of FFP than established clinical predictors, including PSA, T stage, surgical margin status, or Gleason score (P < 0.002). Thirty-two percent of men with a negative PSMA PET result did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59 ng/mL over the 3 y. Conclusion: PSMA PET results are highly predictive of FFP at 3 y in men undergoing sRT for BCR after RP. In particular, men with negative PSMA PET results or disease identified as still confined to the prostatic fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional androgen deprivation therapy than those with extrafossa disease.

Secondary Diffuse Choroid Plexus B-Cell Lymphoma: Case Report and Review of Literature.

BACKGROUND: Central nervous system (CNS) relapse is an uncommon complication of diffuse large B cell lymphoma and is associated with significant mortality and morbidity. It is becoming a more prevalent pathologic entity in the rituximab era. Our case provides insight into the pathophysiology, diagnosis, prevention, and management of secondary intraventricular CNS lymphomas. CASE DESCRIPTION: We report an unusual case of a 64-year-old man who presented with an isolated secondary CNS lymphoma involving the choroid plexus in a diffuse pattern. He initially presented with obstructive hydrocephalus from diffuse choroid plexus lesions and was commenced on systemic therapy after confirmation of diagnosis via samples obtained from an open biopsy. CONCLUSIONS: This case highlights the lack of high-quality evidence behind the use of high-dose intravenous methotrexate as CNS prophylaxis. The case provides additional insight into the pathophysiology of intraventricular CNS lymphomas and the importance of establishing a histopathologic diagnosis via an open biopsy before the administration of high-dose steroids.

Asymptomatic Prostate Cancer Brain Metastases on 68Ga-PSMA PET/CT.

Brain metastases from prostate cancer are rare and occur at a late stage in the natural history of the disease. Men usually present with neurological manifestations. We present a 66-year-old asymptomatic man who had incidental brain metastases detected on Ga-PSMA PET/CT, which was later confirmed on biopsy to be prostate adenocarcinoma. With newer androgen deprivation agents and improved imaging capabilities increasing the mean survival and thus the incidence of brain metastases from prostate cancer, it is important to consider this important differential not only in men who display neurological symptoms but also in men who are asymptomatic.

Results of a Prospective Phase 2 Pilot Trial of 177Lu-PSMA-617 Therapy for Metastatic Castration-Resistant Prostate Cancer Including Imaging Predictors of Treatment Response and Patterns of Progression.

BACKGROUND: 177Lu-PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial. PATIENTS AND METHODS: Men with progressive, symptomatic metastatic castration-resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane-based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no 18F-Fluoro-deoxyglucose (FDG) PET-discordant disease. Men received up to 4 cycles of Lu-PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate-specific antigen (PSA) progression. The study assessed treatment response to Lu-PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment. RESULTS: Fourteen of 18 men screened underwent Lu-PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression. CONCLUSION: PSMA PET plays an important role in predicting treatment response to Lu-PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options.

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade.

Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on 68Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] ± bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial 68Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH ± bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUVmax, SUVmean, and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5-61) reduction in SUVmax was recorded by day 9 after AB. A reduction from baseline SUVmax occurred in 86.5% (6/7) men by day 9 (P < 0.04), with an associated PSA response in 100% men (P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27-97) (P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUVmax in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7-66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUVmax and SUVmean on PSMA PET compared with baseline (P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (-15% [IQR, 70-138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on 68Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.

Tension pneumocephalus from skull base surgery: A case report and review of the literature.

BACKGROUND: Tension pneumocephalus from skull base surgery is a rare occurrence that mandates urgent neurosurgical attention. CASE DESCRIPTION: We describe a case of tension pneumocephalus secondary to an endoscopic endonasal resection of an adamantinomatous craniopharyngioma and how it was successfully managed at our institution. CONCLUSION: Our experience reflects that definitive treatment of tension pneumocephalus is required with multilayered dural repair, but temporising measures should be used immediately to prevent neurological deterioration prior to the definitive repair.

Cerebral abscesses after endovascular coiling of a paraophthalmic aneurysm: Case report and review of the literature.

BACKGROUND: Intracranial infections are a rare complication of therapeutic neuroendovascular procedures. CASE DESCRIPTION: We present a case of a 72-year-old female with multiple unilateral cerebral hemisphere abscesses after endovascular embolization of a right paraophthalmic aneurysm and also provide a comprehensive review of the literature on cerebral abscesses following neurovascular embolization. CONCLUSION: Infection following coil embolization of cerebral aneurysm is rare. However, it is likely to increase in the setting of increased used of neuroendovascular techniques in the future. Therefore, we suggest that extreme care is taken to ensure proper asepsis during embolization, and a high index of suspicion is maintained in patients with predisposing characteristics (large hemorrhage, ischemia, recurrent endovascular procedures, right-to-left shunt, and concomitant infection). Given the fact that the majority of abscesses occurred in patients who have had ruptured aneurysms, we suggest consideration is given to prophylactic intraprocedural intravenous antibiotics use as seen with open aneurysm treatment.