Comparison of 18F-DCFPyL and 68Ga-PSMA-11 for 177Lu-PSMA-617 therapy patient selection.

Purpose: 68Ga-PSMA-11 is recommended for the selection of patients for treatment in the package insert for 177Lu-PSMA-617. We aimed to compare imaging properties and post-treatment outcomes from radioligand therapy (RLT) of patients selected with 68Ga-PSMA-11 and 18F-DCFPyL. Methods: We retrospectively evaluated 80 patients undergoing PSMA RLT, who had pretreatment imaging using either 68Ga-PSMA-11 or 18F-DCFPyL. For both groups, we compared the biodistribution and lesion uptake and the PSA response to treatment. Results: Both agents had comparable biodistribution. Patients initially imaged with 18F-DCFPyL had a higher PSA response (66% vs. 42%), and more patients had a PSA50 response (72% vs. 43%) compared to patients imaged with 68Ga-PSMA-11. Conclusion: 18F-DCFPyL and 68Ga-PSMA-11 had comparable biodistribution and lesion uptake. Patients imaged with 18F-DCFPyL demonstrated clinical benefit to PSMA RLT comparable to those imaged with 68Ga-PSMA-11, and either agent can be used for screening patients.

Assessing Response to PSMA Radiopharmaceutical Therapies with Single SPECT Imaging at 24 Hours After Injection.

Understanding the relationship between lesion-absorbed dose and tumor response in 177Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing 177Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECTmean, SPECTmaximum, and SPECTVIP-PSMA, respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECTmean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECTmaximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECTVIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECTVIP-PSMA response (R 2 = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response (R 2 = 0.05, P = 0.001, and R 2 = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations.

Real-World Experience with 177Lu-PSMA-617 Radioligand Therapy After Food and Drug Administration Approval.

We report our initial real-world experience with 177Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177Lu-PSMA-617 radioligand therapy.

177Lu-PSMA Therapy.

Radiopharmaceutical therapy using 177Lu-prostate-specific membrane antigen (PSMA) is an effective prostate cancer treatment that was recently approved by the U.S. Food and Drug Administration. This method leverages the success of PSMA-targeted PET imaging, enabling delivery of targeted radiopharmaceutical therapy; has demonstrated a clear benefit in large prospective clinical trials; and promises to become part of the standard armamentarium of treatment for patients with prostate cancer. This review highlights the evidence supporting the use of this agent, along with important areas under investigation. Practical information on technology aspects, dose administration, nursing, and the role of the treating physician is highlighted. Overall, 177Lu-PSMA treatment requires close collaboration among referring physicians, nuclear medicine technologists, radiopharmacists, and nurses to streamline patient care.

Igniting activation: Using unannounced standardized patients to measure patient activation in smoking cessation.

INTRODUCTION: Despite a decline, smoking rates have remained high, especially in communities with lower income, education, and limited insurance options. Evidence shows that physician-initiated counseling on smoking cessation is effective and saves lives, and that specific skills are needed to appropriately lead this type of patient-physician communication. Residency is a critical moment for future physicians and may be the optimal time to learn, practice, and refine this skillset. Unannounced Standardized Patients (USPs) have been found to be effective, incognito evaluators of resident practices. METHODS: This study introduced rigorously trained actors (USPs) into two urban, safety-net clinics to assess resident ability to engage, activate, and counsel a pre-contemplative smoker. A complementary chart review assessed appropriate documentation in the patient's electronic health record (EHR) and its relationship to counseling style and prescribing practices. RESULTS: Resident scores (% well done) on patient education and engagement were low (33% and 23%, respectively). Residents who coupled cessation advice with an open discussion style activated their patients more than those who solely advised cessation across all comparable measures. On EHR documentation, residents who accurately documented smoking history were more likely to directly advise their patient to quit smoking when compared to residents who did not document (t(97) = 2.828, p = .006, Cohen's D = 0.56). CONCLUSIONS: Results highlight the need to reinforce training in patient-centered approaches including motivational interviewing, counseling, and shared decision-making. Future research should focus on the effects of smokers in pre-contemplation on physician counseling style and examine the relationship between medical training and provider communication to guide interventions.

"I Cannot Take This Any More!": Preparing Interns to Identify and Help a Struggling Colleague.

BACKGROUND: Few programs train residents in recognizing and responding to distressed colleagues at risk for suicide. AIM: To assess interns' ability to identify a struggling colleague, describe resources, and recognize that physicians can and should help colleagues in trouble. SETTING: Residency programs at an academic medical center. PARTICIPANTS: One hundred forty-five interns. PROGRAM DESIGN: An OSCE case was designed to give interns practice and feedback on their skills in recognizing a colleague in distress and recommending the appropriate course of action. Embedded in a patient "sign-out" case, standardized health professionals (SHP) portrayed a resident with depressed mood and an underlying drinking problem. The SHP assessed intern skills in assessing symptoms and directing the resident to seek help. PROGRAM EVALUATION: Interns appreciated the opportunity to practice addressing this situation. Debriefing the case led to productive conversations between faculty and residents on available resources. Interns' skills require further development: while 60% of interns asked about their colleague's emotional state, only one-third screened for depression and just under half explored suicidal ideation. Only 32% directed the colleague to specific resources for his depression (higher among those that checked his emotional state, 54%, or screened for depression, 80%). DISCUSSION: This OSCE case identified varying intern skill levels for identifying and assessing a struggling colleague while also providing experiential learning and supporting a culture of addressing peer wellness.

Using Unannounced Standardized Patients to Explore Variation in Care for Patients With Depression.

BACKGROUND: Physicians across specialties need to be skilled at diagnosing and treating depression, yet studies show underrecognition and inadequate treatment. Understanding the reasons requires specifying the influence of patient presentation, screening, and physician competence. OBJECTIVE: We deployed an unannounced standardized patient (SP) case to assess clinic screening and internal medicine (IM) residents' practices in identifying, documenting, and treating depression. METHODS: The SP represented a new patient presenting to the outpatient clinic, complaining of fatigue, with positive Patient Health Questionnaire (PHQ) items 2 and 9 and a family history of depression. The SPs assessed clinic screening and IM resident practices; appropriate treatment was assessed through chart review and defined as the resident doing at least 1 of the following: prescribing a selective serotonin reuptake inhibitor (SSRI), making a referral, or scheduling a 2-week follow-up. RESULTS: Of 129 IM residents, 85 (66%) provided appropriate treatment, 79 (61%) appropriately referred, 59 (46%) prescribed an SSRI, and 49 (38%) scheduled a 2-week follow-up, while 40 (31%) did not add depression to the problem list. The IM residents who used PHQ-2 and PHQ-9 were more likely to appropriately (89%) versus inappropriately (50%) treat (P < .001). Compared with those who did not, residents who treated appropriately assessed depression symptoms more (P < .001) and had better communication (73% versus 50%, P = .02), patient centeredness (74% versus 42%, P = .03), and patient activation skills (35% versus 11%, P < .001). CONCLUSIONS: The use of unannounced SPs helps identify targets for training residents to provide evidence-based treatment of depression.

An educational initiative to improve medical student awareness about brain death.

OBJECTIVE: Medical student knowledge about brain death determination is limited. We describe an educational initiative to improve medical student awareness about brain death and assess the impact of this initiative. SUBJECTS AND METHODS: Beginning in July 2016, students at our medical school were required to attend a 90-min brain death didactic and simulation session during their neurology clerkship. Students completed a test immediately before and after participating in the initiative. RESULTS: Of the 145 students who participated in this educational initiative between July 2016 and June 2017, 124 (86%) consented to have their data used for research purposes as part of a medical education registry. Students correctly answered a median of 53% of questions (IQR 47-58%) on the pretest and 86% of questions (IQR 78-89%) on the posttest (p < .001). Comfort with both performing a brain death evaluation and talking to a family about brain death improved significantly after this initiative (18% of students were comfortable performing a brain death evaluation before the initiative and 86% were comfortable doing so after the initiative, p < .001; 18% were comfortable talking to a family about brain death before the initiative and 76% were comfortable doing so after the initiative, p < .001). CONCLUSIONS: Incorporation of simulation in undergraduate medical education is high-yield. At our medical school, knowledge about brain death and comfort performing a brain death exam or talking to a family about brain death was limited prior to development of this initiative, but awareness and comfort dealing with brain death improved significantly after this initiative.