Citations

Purpose: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. Methods: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. Results: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. Conclusion: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

Abstract Background Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment for chronic knee pain. However, there has been minimal investigation of real-world, long-term outcomes and factors that predict treatment success after GNRFA. Objectives To evaluate the effectiveness of GNRFA for chronic knee pain in a real-world population and identify predictive factors. Methods Consecutive patients who underwent GNRFA at a tertiary academic center were identified. Demographic, clinical, and procedural characteristics were collected from the medical record. Outcome data were numeric rating scale (NRS) pain reduction and Patient Global Impression of Change (PGIC). Data were collected by standardized telephone survey. Predictors of success were evaluated with logistic and Poisson regression analyses. Results Of the 226 total patients identified, 134 (65.6 ± 12.7; 59.7% female) were successfully contacted and analyzed, with a mean follow-up time of 23.3 ± 11.0 months. Of those, 47.8% (n = 64; 95% CI: 39.5%–56.2%) and 61.2% (n = 82; 95% CI: 52.7%–69.0%) reported ≥50% NRS score reduction and ≥2-point NRS score reduction, respectively, and 59.0% (n = 79; 95% CI: 50.5%–66.9%) reported “much improved” on the PGIC questionnaire. Factors associated with a greater likelihood of treatment success (P < .05) were higher Kellgren–Lawrence osteoarthritis grade (2–4 vs 0–1); no baseline opioid, antidepressant, or anxiolytic medication use; and >3 nerves targeted. Conclusion In this real-world cohort, approximately half of the participants experienced clinically meaningful improvements in knee pain after GNRFA at an average follow-up time of nearly 2 years. Factors associated with higher likelihood of treatment success were more advanced osteoarthritis (Kellgren–Lawrence Grade 2–4); no opioid, antidepressant, or anxiolytic medication use; and >3 nerves targeted.

Zusammenfassung Hintergrund Aktuell wurde mit dem Tetrafecta-Score das erste Instrument zur Beurteilung der Behandlungsqualität in der chirurgischen Primärtherapie des Peniskarzinoms (PECa) publiziert. Eine externe wissenschaftliche Auseinandersetzung mit den ihn definierenden Einzelkriterien steht bislang noch aus und bildet das Studienziel. Material und Methode Es wurde eine internationale Arbeitsgruppe bestehend aus 12 Urologen und einem Onkologen mit klinischer und akademisch-wissenschaftlicher Expertise auf dem Gebiet des Peniskarzinoms gegründet. In einem modifizierten vierstufigen Delphi-Prozess wurden unter Einbeziehung der Tetrafecta-Kriterien insgesamt 13 Kriterien für PECa-Patienten in den klinischen AJCC-Stadien 1–4 (T1–3N0–3, aber M0) definiert, von denen in einer geheimen Abstimmung jeder der Experten 5 auswählen musste, um dadurch einen individuellen Pentafecta-Score zu generieren. Anschließend wurde das Rating der Experten aggregiert ausgewertet und dadurch ein finaler Pentafecta-Score gebildet. Ergebnisse Keines der ursprünglichen Tetrafecta-Kriterien wurde in den finalen Pentafecta-Score übernommen, der sich aus den folgenden Kriterien zusammensetzt: 1.) Organerhalt, sofern immer möglich (≤T2), jedoch stets unter Wahrung eines negativen chirurgischen Schnittrandes, 2.) beidseitige inguinale Lymphadenektomie (ILAE) ab pT1G2N0, 3.) perioperative Chemotherapie sollte erfolgen, sofern durch die Leitlinien indiziert, 4.) ILAE sollte, sofern indiziert, in einem zeitlichen Abstand von maximal 3 Monaten zur Primärtumorresektion erfolgen und 5.) die behandelnde Klinik sollte im Minimum 15 chirurgische Primärtherapien bei PECa-Patienten durchführen. Nur 7 der 13 Experten (54%) zeigten eine starke Korrelation ihres individuellen mit dem finalen Pentafecta-Score (rsp >0.60). Schlussfolgerung Auf der Basis eines moderierten Abstimmungsprozesses unter internationalen PECa-Experten wurde ein Pentafecta-Score als Qualitätssicherungs-Instrument für die chirurgische Primärtherapie gebildet, der nun anhand von patientenrelevanten und patientenberichteten Endpunkten zu validieren ist.

12057 Background: AlthoughCLL primarily affects older adults (median age 71 years), limited data exists about the outcomes of adults who are ≥80 years old because they are under-enrolled on clinical trials. Methods: The Mayo Clinic CLL Database was used to conduct a retrospective cohort study of adults ≥80 years at the time of frontline CLL treatment. Kaplan-Meier analysis was used to plot OS, and cumulative incidence was used to plot TTNT, accounting for competing risk of death. The Mayo Clinic IRB approved the study. Results: Our study included 216 patients with CLL who were age ≥80 years at the time of frontline CLL therapy between 1/1995 and 11/2022 (Table). The median time from CLL diagnosis to initiation of frontline therapy was 3.1 years. The median OS after start of frontline therapy was 3.9 years. The median OS was 3.3 years (95% CI 2.6–4.2) for patients who received alkylating agents (e.g., chlorambucil, n=96), 3.8 years (95% CI 2.8–not reached [NR]) for purine analogues (e.g., fludarabine, n=11), 3.9 years (95% CI 3.2–4.9) for anti-CD20 monoclonal antibody monotherapy (e.g., obinutuzumab, n=64), and not reached (95% CI 3.3-NR) for novel agents (n=43) (P=0.02). The types of novel agents included ibrutinib (n=19), acalabrutinib (n=16), venetoclax (n=7), and orelabrutinib (n=1). There was no difference in OS between 36 patients who received a BTKi compared to the 7 patients who received venetoclax-based therapy. At a median follow-up time of 6.7 years from the first visit, 143 patients died from the following: progressive CLL (n=63), infections (n=12), other cancer (n=11), non-CLL reasons (n=21). Cause of death was unavailable for 36 patients. On multivariable analyses, older age (i.e., any 5-year increase in age) was associated with a 50% increased risk of death (HR 1.5, 95% CI 1.2-1.9, p=0.001), and treatment with non-novel agents was associated with 3.2 times increased risk of death (HR 3.2, 95% CI 1.2-8.9, p=0.02). Of the 216 patients, 76 patients required second-line therapy; the median TTNT was 4.2 years (95% CI 2.9-NE). The most used second-line agents were monoclonal antibodies alone (20/76, 26%) and single-agent alkylators (18/76, 24%). Conclusions: When compared to all other CLL treatments, novel agents such as BTKi and venetoclax-based treatments are associated with significantly improved OS in patients with CLL ≥80 years old when used in the frontline setting. [Table: see text]

7577 Background: Prior research has consistently shown that patients with chronic lymphocytic leukemia (CLL) have an ~2-fold increased risk of developing melanoma compared to controls. MBL is a common condition affecting 8-10 million adults over the age of 40 years in the United States and is a precursor to CLL. Little is known about the association between MBL and melanoma. Herein, we evaluated the risk of incident melanoma in a large cohort of individuals screened for MBL. Methods: Participants from the Mayo Clinic Biobank who had no prior history of hematologic malignancy, were 40 years or older, were residents of counties surrounding Mayo Clinic, and who provided blood samples between 7/2009 and 4/2022 were included in the study. Peripheral blood mononuclear cells were screened for MBL using highly sensitive eight-color flow cytometry. Individuals with MBL were classified as CLL-like MBL (CD5+, CD20dim) or atypical MBL (CD5+, CD20+) based on immunophenotypes, and also classified as low-count MBL (LCMBL) or high-count MBL (HCMBL) based on whether the percent clonal B-cell count was < 85% or ≥85%, respectively. Diagnosis of melanoma was ascertained using ICD codes and review of the electronic health records. All individuals were followed from date of sample upon which MBL screening was performed to the earliest of incident melanoma, loss to follow-up, withdrawal from the study, or September 30, 2022. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age, sex, and history of melanoma in previous 5 years. Results: A total of 7,334 participants were screened for MBL, of which 1,151 (16%) individuals had MBL. Among those with MBL, 1,107 (96.2%) had CLL-like MBL and 1098 (95.4%) had LC MBL. The median age at entry into the MBL screening cohort was 67 years (range 40-101) and 37% were male; individuals with MBL were older (median age 72 vs 65 years) and male (49% vs 35%). After a median follow-up of 2.9 years (range 0-13.2), 121 of the 7,334 (1.6%) participants developed incident melanoma after the date of MBL screening. The 10-year cumulative incidence of melanoma among individuals with MBL was 7.8% (95% CI 4.5-13.5%) compared to 3.4% (2.7-4.4%) in those who screened negative for MBL. After adjusting for age, sex, and history of prior melanoma, we found a 1.81-fold increased risk of incident melanoma (95% CI 1.19-2.76) among individuals with MBL. The increased risk of melanoma persisted when the analysis was restricted to individuals with LCMBL (HR = 1.84; 95% CI 1.21-2.82). Conclusions: In the largest MBL screening cohort to date, we found that LCMBL, a common condition, was associated with an 84% elevated risk of melanoma, similar to the ~2-fold increased risk observed in patients with CLL. These data, together with our prior findings of a heightened risk of serious infections and lymphoid malignancies, suggest that individuals with LCMBL are at increased risk for adverse health outcomes.

5512 Background: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (HR = 0.57, one-sided log-rank p = 0.044, which met the one-sided significance level of 0.1 used for sample size calculation). Final overall survival (OS) and corresponding biomarker analyses are reported here. Methods: Patients (pts) with platinum-resistant high-grade serous ovarian cancer and unlimited previous lines of cytotoxic therapy in the platinum-sensitive setting but no more than one line of cytotoxic therapy in the platinum-resistant setting, were randomized 1:1 to gemcitabine/berzosertib versus gemcitabine alone. Randomization was stratified based on platinum free interval (PFI), PFI≤3 months versus > 3 months. Crossover from gemcitabine to gemcitabine/berzosertib was allowed upon disease progression by RECIST 1.1. OS was a secondary endpoint while preplanned exploratory correlative studies included assessment of DNA repair pathways and replication stress (RS) alterations by targeted gene sequencing and/or immunohistochemistry (IHC). Results: Seventy pts were randomly assigned to treatment with gemcitabine/berzosertib (34 pts) or gemcitabine alone (36 pts); 15 pts crossed over from gemcitabine to gemcitabine/berzosertib. At the final OS analysis (92.9% maturity), median follow-up was 53.2 weeks in the gemcitabine/berzosertib and 43 weeks in the gemcitabine alone groups. Median OS in the intent-to-treat (ITT) population was 59.4 weeks in the gemcitabine/berzosertib group versus 43.0 weeks in the gemcitabine alone group (HR 0.79, 90% CI 0.52-1.2, one-sided p = 0.18). However, when patients who crossed over to gemcitabine/berzosertib were excluded from analysis, a significant OS benefit was observed with gemcitabine/berzosertib (HR 0.60, 90%CI 0.37−0.97); HR was 0.26 (90% CI 0.1−0.7) in pts with PFI≤3 months and 0.89 (90%CI 0.50−1.59) in pts with PFI > 3 months. Furthermore, significant OS benefit was observed in pts with RS-low tumors (HR 0.39, 90%CI 0.17−0.91, defined as tumors harboring no genomic RS alterations related to loss of RB pathway regulation and/or oncogene-induced RS) but not in pts with RS-high tumors (HR 0.74, 90%CI 0.35−1.56). Additional targeted gene sequencing and IHC analyses as well as analyses adjusting for patient crossover will be reported at the meeting. Conclusions: In the ITT population, gemcitabine/berzosertib did not significantly improve OS versus gemcitabine alone. Pts with PFI≤3 months and pts with RS-low tumors may derive a survival advantage from addition of berzosertib to gemcitabine in the platinum-resistant setting. Clinical trial information: NCT02595892 .

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

AbstractThis meta‐analysis investigated the effects of exercise on Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores following vertebroplasty or kyphoplasty in osteoporotic fractures. A literature search of PubMed, EMBASE (Elsevier), CiNAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 6, 2022. Eligible studies reported osteoporosis patients over 18 years of age with a diagnosis of at least one vertebral fracture via radiography or clinical assessment. This review was registered in PROSPERO (ID: CRD42022340791). Ten studies met the eligibility criteria (n = 889). VAS scores at baseline were 7.75 (95% CI: 7.54, 7.97, I2 = 76.11%). Following initiation of exercise, VAS scores at the endpoint of 12 months were 1.91 (95% CI: 1.53, 2.29, I2 = 92.69%). ODI scores at baseline were 68.66 (95% CI: 56.19, 81.13, I2 = 85%). Following initiation of exercise, ODI scores at the endpoint of 12 months were 21.20 (95% CI: 14.52, 27.87, I2 = 99.30). A two‐arm analysis demonstrated improved VAS and ODI for the exercise group compared to non‐exercise control at 6 months (MD = −0.70, 95% CI: −1.08, −0.32, I2 = 87% and MD = −6.48, 95% CI: −7.52, −5.44, I2 = 46%, respectively) and 12 months (MD = −0.88, 95% CI: −1.27, −0.49, I2 = 85% and MD = −9.62, 95% CI: −13.24, −5.99, I2 = 93%). Refracture was the only adverse event reported and occurred almost twice as frequently in the non‐exercise group than in the exercise group. Exercise rehabilitation post vertebral augmentation is associated with improved pain and functionality, particularly after 6 months of exposure, and may reduce refracture rate.