Citations

129 Background: Few studies have explored the use of focal therapies to address select sites of resistant disease in men receiving 177-Lu-PSMA-617 for metastatic castrate resistant prostate cancer (mCRPC). Our institutional practice is to offer SBRT for patients with up to 5 sites of oligoprogression or non-responding lesions while undergoing 177Lu-PSMA-617 (every 6 weeks for 6 cycles total). This is determined by PSMA or choline PET imaging during the course of 177Lu-PSMA-617. Herein, we evaluated the safety of adding target SBRT during treatment with 177Lu-PSMA-617. Methods: This retrospective single institution analysis was conducted via systematic chart review to evaluate for adverse events during or after treatment. Grading of treatment-related adverse events was conducted using Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5). Results: Thirty-one patients receiving 177Lu-PSMA-617 with 51 sites of oligoprogressive or non-responding metastatic disease were treated with SBRT. The median number of sites treated was 1 (range 1-4). Most patients received SBRT immediately after cycle 6 (32%) or after cycle 3 or 4 (42%). Bone was the most commonly treated site of disease (90%) with the majority (54%) of bone sites being spine or sacrum, followed by lymph nodes (10%). Ultimately, 84% of patients completed all 6 cycles of 177Lu-PSMA-617 (range 4-6). The median follow-up time was 19.1 months (IQR 15.5-22.4) after 177Lu-PSMA-617 therapy start. A total of 2 patients experienced a pathologic fracture within the SBRT treatment field that could possibly be related to radiotherapy. One patient experienced a grade 2 neuropathy which may have been related to radiation therapy. Other potential adverse events are listed (Table). Conclusions: Our data demonstrates a low rate of significant toxicity with the use SBRT during treatment with 177Lu-PSMA-617. Further study is indicated to determine the oncologic efficacy and potential late side effects of this treatment strategy. Adverse events. Event All Grades Grade > 3 Any Adverse Event 104 2 Anemia 29 (94%) 0 Low Platelets 11 (35.5%) 1 (3.2%) Any Pathologic Fracture 7 (22.5%) 1 (3.2%) Possible SBRT-related Pathologic Fracture 2 (6.5%) 1 (3.2%) Bone Pain Flare 3 (9.6%) 0 Neuropathy 1 (3.2%) 0

424 Background: Advances in prostate cancer (PC) care have led to a 98% 10-year survival rate. Prostate Specific Antigen (PSA) is the primary method of follow-up after definitive radiotherapy (RT), with benign PSA ‘bounce’ occurring in up to 30% of patients, causing uncertainty and anxiety. Distinguishing between PSA bounce and biochemical recurrence (BCR) remains challenging. The Phoenix Criteria is the standard definition of BCR since 2006, defined as PSA nadir + 2 ng/dl, but does not consider patient specific information. Our study aims to explore factors associated with bounce and BCR and develop a predictive tool to differentiate between these two events. Methods: PC patients who received RT at our institution between 2006 and 2022 were identified, including only patients with a PSA increase during follow-up. Exclusion criteria included palliative RT, prostatectomy, or insufficient follow-up information. Patients’ clinical data was collected, and PSA increase was classified as bounce or BCR. Variables were compared using Kruskal Wallis or Chi-square. Multivariate logistic regression was performed in the subset of patients with absolute PSA value >2 (n= 581). Results: Of 1783 patients reviewed due to PSA rise after treatment, 694 met the inclusion criteria. There were 213 (30.7%) with PSA bounce and 481 (69.3%) with recurrence. Prior to meeting the Phoenix Criteria, 20 (4.2%) had biopsy-proven recurrence and 18 (3.7%) imaging-proven recurrence. The median delta PSA was 0.8 ng/mL for bounce vs 5 ng/mL for recurrence (p<0.001). The median time from treatment to event was 14.4 months for bounce vs 45.3 months for BCR (p<0.001). Recurrence was significantly associated (p<0.001) with older age at diagnosis, N1 stage, higher risk category, Gleason score, and higher baseline PSA. In the subgroup of patients without ADT, recurrence was associated with a lower median first PSA post-RT (1.9 vs. 2.4, p=0.046) and a lower median nadir before event (0.6 vs. 1.8, p<0.001). Multivariate logistic regression achieved an accuracy of 0.94, with a sensitivity of 0.83, specificity of 0.98, and an area under the curve (AUC) of 0.97. Conclusions: Our results highlight significant differences in clinical factors between bounce and recurrence in post-RT patients. The multivariate logistic regression differentiated the events with 94% accuracy for patients with a rising PSA value >2 subgroup. We highlight the possible improvement that could be accomplished by personalizing a PSA threshold for recurrence versus the Phoenix definition. This tool offers patients and providers a highly specific tool to differentiate between PSA recurrence and bounce, and may reduce stress and unnecessary testing, or help diagnosis recurrence faster. Next steps include prospective validation of the model to assess the impact on clinical practice costs, patient experience, and cancer outcomes.

This Viewpoint advocates for prompt aortic valve replacement (rather than clinical surveillance) as the default strategy for patients with asymptomatic severe aortic stenosis.

PURPOSE Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients' survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease–negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed/refractory (RR) MM. PATIENTS AND METHODS Individual patient data from 20 randomized multicenter trials were collected. Eleven studies (4,773 patients) with sufficient data were analyzed to evaluate whether 9- or 12-month MRD-CR classified at a 10 –5 threshold could be reasonably likely to predict the clinical benefit of new agents regarding PFS and OS. Global odds ratio (OR) was estimated using the bivariate Plackett Copula model. Supportive evaluation included correlations of the treatment effects on MRD-CR end points and PFS/OS, evaluated by both linear regression ( R 2 weighted least squared ) and Copula ( R 2 Copula ) models. RESULTS The analysis demonstrated that both 9- and 12-month MRD-CR strongly correlated with PFS at patient level in NDTE patients, NDTinE patients, and patients with RRMM. Global ORs ranged from 3.06 to 16.24, all with 95% CIs excluding 1.0. Encouraging trial-level correlations ( R 2 , 0.61-0.70) were observed by pooling three populations and were stronger ( R 2 , 0.67-0.78) in the ND population. Similar results were observed for OS. CONCLUSION Our findings provided the support for use of MRD-CR classified at a 10 –5 threshold at either 9 or 12 months after starting of the treatment, as an intermediate end point to support accelerated approvals, in future trials in NDTE patients, NDTinE patients, and patients with RRMM.

We present an 81-year-old male with an extensive past medical history and an enlarging abdominal aortic aneurysm (AAA). Axial imaging showed dense aortoiliac calcification with a complete occlusion of the right common iliac and high-grade stenosis of the left common iliac artery (CIA). Shockwave Intravascular Lithotripsy and the pave-and-crack technique utilizing an endoconduit were used to dilate the left external iliac artery and the CIA to facilitate placement of an aortic stent graft and exclude the patient’s AAA. This method gives surgeons the ability to treat patients with AAAs endovascularly, despite a heavily diseased and/or diminutive iliac anatomy. We also present a contemporary literature review of the utilization of the pave-and-crack technique as well as tips and tricks of how we do it.

Purpose: To understand the current state of epilepsy surgery education delivered to epilepsy fellows in the United States. Methods: An online survey focused on characteristics of epilepsy surgery education was distributed to all 93 epilepsy fellowship program directors listed on the ACGME website (accessed in May 2022). Programs were stratified per the number of fellows currently enrolled: 0 to 3 (group A) and ≥4 (group B). Results: Forty-one of 93 (44%) epilepsy fellowship programs were included in the study. The average number of resective surgeries, ablations, or corpus callosotomies per year was mostly 0 to 30 (54%) in group A and mostly >30 (80%) in group B ( P = 0.05). The average number of intracranial implantations per year was mostly 0 to 20 (58%) in group A and mostly >20 (80%) in group B ( P < 0.05). The average number of neurostimulation implantations per year was 15 (range 0–90; vagal nerve stimulation), 7 (range 0–25; responsive neurostimulation), and 4 (range 0–10; deep brain stimulation). In 78% of programs, fellows are not required to present a minimum number of epilepsy surgery cases in multidisciplinary conference before graduation. Roughly half of programs (51%) reported not using objective measures to assess fellow competency in epilepsy surgery. Conclusions: Our results suggest significant variability in epilepsy surgery volume and, consequently, fellow exposure to surgical cases and lack of standardized, objective measures in fellow teaching and assessment in the field of epilepsy surgery across programs in the United States. We advocate development of a core epilepsy surgery curriculum including minimum standards at the national level.

Purpose To establish consensus statements via a modified Delphi process about ethics, transparency, regulation, and best practices for the use of orthobiologics in clinical practice for musculoskeletal pathology. Methods A consensus process on the regulation of orthobiologics at the provider level was conducted using a modified Delphi technique. Twenty orthopaedic surgeons, sports medicine physicians, or basic scientists participated. Each participant was a Biologic Association member organization representative and asked to participate because of their active interest in the field of orthobiologics. Levels of consensus were delineated according to the number of votes for each statement: no consensus, <80%; consensus, 80% to 89%; strong consensus, 90% to 99%; unanimous, 100%. Results The 26 consensus statements on orthobiologics resulted in 14 achieving unanimous consensus, 8 achieving strong consensus, 3 achieving consensus, and 1 did not achieve consensus. Overall, 85% of the statements reached either a unanimous or strong consensus. Of the statements regarding communication and transparency, 9 reached unanimous consensus, including information to convey and helpful tools to describe current orthobiologics, persistent misinformation, use of the word “stem cells,” “off‐label” use, and problems with the present regulatory environment. Five statements discussing the regulation of novel orthobiologics achieved unanimous consensus. These statements highlighted research regulation, safety, and suggested improvements to regulatory issues. The statement that did not achieve any consensus was on the regulatory processes that should be in place by an institution providing novel orthobiologic treatments. No statement reached a unanimous agreement on cost or ethical considerations. Conclusions This study successfully identified key consensus statements emphasizing the importance of ethics, transparency, and regulation in the use of orthobiologics, with 85% of statements reaching unanimous or strong consensus. These findings underscore the need for standardized communication, improved regulatory frameworks, and enhanced safety measures while highlighting persistent challenges in addressing cost and ethical considerations. Level of Evidence Level V, expert opinion.