Faculty Bibliography

This guideline summarizes updated safety data (2017-2025) and provides expert recommendations on the use of low intensity transcranial electrical stimulation (tES) in humans. tES encompasses several techniques including transcranial direct current stimulation (tDCS), oscillatory transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial temporal interference stimulation (tTIS), and their combinations or variations. Across over 300,000 sessions involving healthy individuals, patients with neuropsychiatric conditions, and other clinical populations, no tES-related serious adverse events (AEs) have been reported. Moderate AEs are rare and limited to a small range of specific applications. Mild AEs are common and include transient symptoms such as localized sensations (e.g., tingling or burning), headaches, and fatigue. Similar mild AEs are also reported by individuals receiving placebo stimulation. The frequency, magnitude, and type of AEs are comparable across healthy, clinical, and vulnerable groups, including children, elderly, or pregnant women. Combined interventions (e.g., co-application with EEG, TMS, or neuroimaging) have not shown increased safety risks. Safety is well-established for both bipolar and multichannel tES when applied up to 4 mA and up to 60 min per day. Higher intensities and longer stimulation durations may also be safe. Nevertheless, the number of studies using intensities above 4 mA or stimulating longer than 60 min is low. Home-based use of treatments is growing rapidly, leveraging remote supervision to provide patients with greater access and enable repeated, sustained dosing paradigms. We recommend using screening and AE questionnaires in future controlled studies, in particular when planning to extend the stimulation parameters applied. We discuss recent regulatory and ethical issues.

Cervical spondylosis is a broad term that describes pathological degeneration of the cervical spine, leading to axial neck pain, cervical myelopathy, and radiculopathy. Surgical treatments have been developed to address cervical radiculopathy and myelopathy, with the gold standard being anterior cervical diskectomy and fusion (ACDF). However, cervical fusion is associated with many well-known complications, such as pseudarthrosis and adjacent segment disease (ASD). As a result, cervical disk arthroplasty (CDA) was developed as an alternative to fusion for addressing cervical pathology without the risk of pseudarthrosis while preserving mobility and theoretically decreasing the risk of ASD. CDA, however, is uniquely associated with heterotopic ossification formation. While ACDF remains the gold standard, newer studies with long-term follow-up extending up to 20 years have begun to demonstrate superiority of CDA over ACDF, with lower rates of ASD. While the success of CDA is leading to a change in practice patterns, there is still a role for fusion in the management of cervical disease.

BACKGROUND:The purpose of our study was to compare patient-reported outcomes at 6-month follow-up between primary hip arthroscopy patients who were partial weight bearing on crutches for 4 weeks vs. 1 week postoperatively. METHODS:We conducted a pseudorandomized clinical trial involving patients who underwent arthroscopic treatment of femoroacetabular imipingement at a single center from September 2020 to April 2021. Subjects aged 18-65 years old were alternately assigned to one of the 2 rehabilitation regimens involving either 4-week or 1-week partial weight bearing on crutches. Subjects completed the modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) surveys before surgery and at 6-month follow-up. Achievement of the minimum clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptom state (PASS) was assessed using published mHHS cutoff values. Outcomes were compared between groups with the Mann-Whitney U test and analysis of covariance, while MCID, SCB, and PASS rates were compared with the Fisher exact test. P-values < .05 were considered significant. RESULTS:Fifty patients were included in the study of whom 28 (56.0%) were assigned to 4-week crutch use and 22 (44.0%) to 1-week crutch use. The 4-week crutch use group was significantly older on average (38.4 vs. 32.1 years, P = .03) and had significantly higher mean body mass index (27.6 vs. 24.5, P = .01), but there were no significant baseline differences between the 2 groups (P > .05). After adjusting for age and body mass index, there was no significant difference in preoperative to postoperative improvement in mHHS (P = .43) or NAHS (P = .46) between the 2 groups at 6-month follow-up. Furthermore, there were no significant differences in achievement rates for MCID (P = .50), SCB (P = .51), or PASS (P = .77) between the 2 groups. CONCLUSION/CONCLUSIONS:We identified no significant differences in improvement of mHHS and NAHS or achievement of the MCID, SCB, or PASS at 6-month follow-up between patients on crutches for 4 weeks vs. 1 week postoperatively. LEVEL OF EVIDENCE/METHODS:II, Pseudorandomized clinical trial.

Management of first-time shoulder dislocations in young active patients presents a significant challenge due to the high likelihood of recurrent anterior shoulder instability. Repeated instability events can result in poor outcomes because each dislocation contributes dose-dependent damage to the glenohumeral joint. Various validated techniques are available for reducing glenohumeral dislocations. For in-season athletes sustaining a shoulder dislocation, management requires balancing a rapid return to play with the heightened risk of recurrent instability. In-season surgical management is typically reserved for athletes experiencing recurrent instability or substantial osseous deficits. When surgical intervention is necessary, the approach is guided by the extent of critical glenoid bone loss and whether the humeral head bone defect engages with the glenoid.

BACKGROUND:Preliminary data from the MorningSun study have demonstrated that outpatient subcutaneous mosunetuzumab can be safely administered. AIMS/OBJECTIVE:This publication describes how community centers in the MorningSun phase 2 study of outpatient subcutaneous mosunetuzumab in B-cell non-Hodgkin lymphomas prepared workflow and logistics (staff coordination, practice networks, and patient support) to monitor patients for cytokine release syndrome (CRS) and other toxicities. MATERIALS AND METHODS/METHODS:Ten investigators at US community practice study sites (one rural, seven urban, and two rural/urban) were interviewed between January 12 and February 22, 2024. Interview transcripts were analyzed qualitatively to identify key themes. RESULTS:Prior to the study, 7/10 had limited/no experience administering bispecific antibodies for lymphoma. Regarding preparation before treatment, staff education was the most frequent need (7/10). All sites provided in-service training for staff involved with treatment administration. Most respondents (6/10) had multidisciplinary plans and agreed these eased logistical concerns. Out of hours, patients either called the triage team, a dedicated on-call number, the physician, or the emergency department. Most practices had preexisting relationships with hospitals for CRS management. All practices established methods for outpatient CRS monitoring; patient education and caregivers played important roles, and all respondents encouraged patients to use self-monitoring devices. Each community practice had different workflow and logistics based on their setting and infrastructure. CONCLUSION/CONCLUSIONS:Community practices can leverage other sites' experiences and adopt an individualized approach to implementing bispecific antibodies safely and efficiently. Designating a physician champion could provide a local resource to address staff questions and concerns.

PURPOSE/OBJECTIVE:Cryotherapy is an effective mucositis intervention for selected chemotherapy regimens, but reliance on ice chips has limited its applicability. Our objective was to assess the efficacy and tolerability of a reusable, self-contained, device as an alternative delivery mode. METHODS:A total of 164 patients randomized 2:1 received the device (Chemo Mouthpiece; CMP]) + best supportive care (BSC) (arm A) or BSC only (control, arm B), across 16 study sites. Inclusion criteria allowed broad tumor diagnosis and chemotherapy regimens. During the first two cycles of treatment, patients completed daily questionnaires in which they graded oral pain (OP) and analgesic use (AU) to control mouth pain. A questionnaire assessed device tolerability at the trial's end. RESULTS:The majority of patients received chemotherapy for breast cancer (arm A 52.7%, arm B 61.1%). Colorectal cancers were the next most common diagnosis. The percentage of visits in which any OP (> 0) in cycles 1 and 2 was reported was less among device-using individuals (CMP 17.8% vs Control 24.6%; p < 0.001). Whereas 26% of controls (arm B) required analgesics during their two cycles of treatment, the frequency was 11.3% among arm A (p = 0.01). Arm B AU was reported in 7.7% of visits compared to 1.8% of arm A visits (p < 0.001). End-of-study assessments of device tolerability were favorable. CONCLUSIONS:CMP use for 14 days following chemotherapy infusion mitigated chemotherapy-associated OP and AU. The effect was seen over two cycles of treatment with known stomatotoxic agents having both short and long half-lives. The device was well tolerated. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov (NCT04595838) Posted August 31, 2020.

BACKGROUND/UNASSIGNED:Discovery and incorporation of predictive and prognostic biomarkers enhance outcomes for patients with cancer. Clinico-genomic datasets, which retrospectively link real-world clinical data to tumor sequencing data, are important resources for biomarker research, which has historically relied on robust research infrastructures exclusive to large academic centers. The objective was to evaluate the feasibility of a pragmatic, technology-enabled platform at community-based research sites for development of a prospective clinico-genomic database supported by centralized electronic health record (EHR)-based patient ascertainment and data processing. METHODS/UNASSIGNED:Adults with stage IV or recurrent metastatic non-small cell lung cancer or extensive-stage small-cell lung cancer were enrolled at 23 US sites upon initiating a standard line of therapy. Enrollment rates were estimated from eligible populations at individual centers. Clinical data from routinely collected EHR documentation were centrally processed and normalized for quality control. Serial blood samples at pre-specified timepoints (baseline, during treatment and at disease progression/end of therapy) were used for circulating tumor DNA (ctDNA) genomic profiling. RESULTS/UNASSIGNED:Between December 2019 and May 2021, 944 patients enrolled, representing ≈25 % of eligible patients. Eight-hundred seventeen of 944 (87 %), 406 of 606 (67 %) and 398 of 852 (47 %) participants provided qualifying samples for ctDNA testing at baseline, during treatment and at disease progression/end of therapy, respectively. Samples were provided at all three timepoints by 35 % of participants. CONCLUSION/UNASSIGNED:A community-based oncology patient cohort was rapidly enrolled, creating a real-world clinico-genomic dataset. This pragmatic study platform has potential research applications where prospective real-world data may contribute to evidence generation.

BACKGROUND:Next-generation sequencing (NGS) testing in patients with metastatic non-small cell lung cancer (mNSCLC) identifies actionable driver oncogenes (ADO) and targeted treatment (TT). Potential inequities were evaluated in NGS testing and TT in patients with mNSCLC. PATIENTS AND METHODS/METHODS:This retrospective study used a nationwide electronic health record-derived deidentified database for patients ≥18 years diagnosed with mNSCLC between 4/2018 and 4/2024, ≥2 recorded visits, and follow-up ≥90 days post diagnosis. For TT, patients must have received NGS testing before first-line (1L) treatment and harbored ≥1 1L ADO. RESULTS:A total of 15 392 patients with mNSCLC were included: 66% with commercial insurance, 16% with Medicare, 12% with other, 4% with Medicaid, and 3% with other government insurance. Patients with commercial insurance had significantly higher odds of receiving NGS testing vs Medicare, Medicaid, or other insurance. While patient characteristics varied across insurances, the effect of insurance type on NGS testing did not differ by race/ethnicity, age, or socioeconomic status (SES). Site of care was a significant effect modifier, with increased odds of NGS testing for community vs academic settings for commercial, Medicare, and other insurance and decreased odds for Medicaid. When all patients received NGS testing, significantly lower odds of receiving TT occurred for patients with SES 2 vs SES 1 (lowest); higher odds occurred for Asian vs white patients. CONCLUSION/CONCLUSIONS:Insurance is a key contributor to inequity in NGS testing. When all patients received NGS testing, equity was achieved in patients receiving TT, except those with lower SES, who potentially did not qualify for Medicaid.

INTRODUCTION/UNASSIGNED:Circulating tumor DNA (ctDNA) monitoring is emerging as a minimally invasive complement to tumor imaging. We evaluated the validity of tissue-agnostic ctDNA quantification across four treatment modalities in NSCLC and SCLC. METHODS/UNASSIGNED:Data from consenting patients were collected from electronic health records as part of the Prospective Clinico-Genomic study (NCT04180176). ctDNA tumor fraction (TF) was retrospectively calculated for plasma collected six to 15 weeks after therapy initiation. TF dynamics were compared among an exploratory cohort, NSCLC and SCLC validity cohorts, and by therapy class. RESULTS/UNASSIGNED:In on-treatment plasma, undetectable TF was associated with longer real-world progression-free survival and real-world overall survival in exploratory (21.8 versus 8.8 mo; hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.24-0.50), validity NSCLC (23.5 versus 9.5 mo; HR = 0.34, 95% CI: 0.22-0.53), and validity SCLC (15.9 versus 8.3 mo; HR = 0.19, 95% CI: 0.08-0.42) cohorts. Equal to or greater than 90% and equal to or greater than 50% TF reduction from baseline was also associated with significantly improved outcomes. ctDNA dynamics differed by treatment class: TF reported greater discriminatory power for selecting tumor responses to immunotherapy and targeted therapy (≥50% decrease in 91% of responders versus 24% of nonresponders) than chemotherapy and chemo-immunotherapy (86% versus 60%). TF dynamics correlated with outcomes, but models of real-world progression-free survival and real-world overall survival were improved when tumor response was included. CONCLUSIONS/UNASSIGNED:Tissue-agnostic monitoring of molecular response on the basis of ctDNA TF dynamics has utility in the real-world setting across four different treatment regimens. These results suggest that ctDNA dynamics may be complementary to tumor imaging in both NSCLC and SCLC to better inform patient care.