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Abstract Background and Objectives Lucid episodes (LEs) in people living with late-stage dementia have been reported anecdotally. However, how this seemingly unexpected phenomenon is experienced by family caregivers is less known. Focusing on the two most common groups of informal caregivers, spouses and adult children, this study examined variability in family caregivers’ experiences with LEs—whether they exhibit differential appraisals of and responses to LEs. Research Design and Methods Using a sample of former/bereaved and current family caregivers from UsAgainstAlzheimer’s A-LIST, we conducted an online survey of spouse and child caregivers (N = 387). We conducted semistructured interviews among a subset of caregivers who witnessed a LE (n = 22). Results Overall, child caregivers were more likely to witness a LE than spouse caregivers. Among former/bereaved caregivers who witnessed a LE (n = 139), spouses were likely to report nonverbal communication during LEs, appraise LEs more negatively, and make changes in care decisions, such as end-of-life planning and financial decisions, compared to adult children. Among current caregivers who witnessed a LE (n = 80), spouses often reported no special circumstances preceding LEs, whereas children linked LEs to friend/family visits. No significant differences were found in positive and negative appraisals of LEs between current spouse and child caregivers. Content analysis of qualitative interviews revealed the contexts underlying these differences. Discussion and Implications Differences between spouses and adult children in their experiences with LEs are related to their different caregiving contexts, including relationship history, living arrangements, expectations, motivations, and caregiving resources.

Abstract Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.

6061 Background: PDS0101 is a T cell stimulating immunotherapy (therapeutic vaccine) targeting HPV16. The combination of PDS0101 + pembrolizumab (5 cycles) has shown durable clinical responses in HPV-positive recurrent/metastatic HNSCC. MC200710 is a window of opportunity study in patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). This prospective phase II trial utilized 2 cycles of neoadjuvant PDS0101 aloneor in combination with pembrolizumab prior to surgical resection or chemoradiotherapy (CRT). Herein, we report the initial results, including primary endpoint of ctDNA response. Methods: Between June 2022 and September 2024, 20 patients (10 per Arm) with locally advanced HPV+ OPSCC were enrolled in a sequential alternating design. Arm A received 2 cycles of PDS0101 and Arm B received 2 cycles of PDS0101 and pembrolizumab with all patients undergoing subsequent surgery or CRT. Assessments were done at baseline, post cycle 1, and post cycle 2 (prior to surgery or CRT). The coprimary endpoint of ctDNA response was defined as a ≥50% decline in ctDNA post cycle 2 compared to baseline as quantified using NavDx (TTMV fragments/mL). Radiologic objective response rate (ORR) was assessed as per RECIST 1.1. Toxicity through the neoadjuvant period was assessed using CTCAE criteria and recurrence rates following surgery or CRT are reported. Results: Patients were similar between arms: male 90%, median age 61 years, cT1/T2 70%, cN1 65%, and no smoking history 65%. All patients completed both cycles of therapy with 13 (65%) undergoing primary operative management and 7 CRT (35%). The most common toxicity was injection site reaction 85% grade 1, 15% grade 2, 0% grade 3, consistent with prior studies. One patient experienced grade 2 pneumonitis during the neoadjuvant window (Arm B). There was one grade 3 toxicity (5%) possibly attributable to study intervention with one patient experiencing transient hepatitis requiring hospitalization (Arm A). Zero of 10 patients in Arm A had a ≥50% decline in ctDNA from baseline while 5 of 10 patients (50%) met this primary endpoint in ARM B (p=0.03). After Cycle 2, based on RECIST 1.1, no Arm A patients had a partial response (PR), with 7 having stable disease (SD); Arm B had 2 patients with PR and 8 with SD. With median follow up of 6 months, 2 patients in Arm A recurred and 0 patients in Arm B. Conclusions: The combination of PDS0101 and pembrolizumab met the trial’s primary endpoint of ctDNA response and shows promise for further evaluation. ctDNA can be used to assess early response and future studies could use ctDNA to adapt neoadjuvant therapy. Based on these findings, a neoadjuvant dose optimization study in HPV16+ oropharyngeal carcinoma is warranted and evaluation of PDS0101 and pembrolizumab in comparison to pembrolizumab alone. Clinical trial information: NCT05232851 .

ImportanceThe De-escalated Adjuvant Radiation Therapy (DART) phase 3 randomized clinical trial (RCT) showed that in patients with human papillomavirus (HPV)−associated oropharyngeal squamous cell carcinoma, postoperative minimal residual disease (MRD), detected through circulating tumor HPV DNA (ctHPVDNA), was associated with a higher risk of disease progression. When considered along with pathologic factors, postoperative ctHPVDNA assessment may improve patient selection for adjuvant treatment de-escalation; however, more data are needed to demonstrate how it may be used in personalizing treatment intensity.ObjectiveTo determine the association of postoperative MRD status with progression-free survival (PFS) after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Design, Setting, and ParticipantsThis was a secondary analysis of the DART RCT, which was conducted from October 2016 to August 2020 in multiple sites in the US. Participants from the de-escalated adjuvant radiation therapy group and the standard of care group with available blood specimen data were included. Reports from 3-month posttreatment surveillance visits were used to assess associations and outcomes. Data analyses were performed from March 2023 to March of 2025.InterventionsThe DART group received 30 to 36 Gy of radiation therapy in 1.5 to 1.8 Gy twice daily, plus docetaxel, 15 mg/m2, on days 1 and 8. The standard of care group received 60 Gy with or without weekly cisplatin, 40 mg/m2.Main Outcome and MeasurePFS.ResultsThe analysis included 140 patients (mean [SD] age, 59.1 [8.4] years; 12 [8.6%] females and 128 [91.4%] males; 97 [69.3%] with no smoking history); characteristics were similar to the overall DART RCT population. Of these, 17 patients (12.1%) had postoperative MRD (13 of 96 [13.5%] receiving DART and 4 of 44 [9.1%] receiving standard of care). For all patients, postoperative MRD positivity was strongly associated with worsened PFS at 24 months (MRD positivity, 69.5%; MRD negativity, 95.9%; hazard ratio [HR], 0.19; 95% CI, 0.06-0.59). MRD positivity was associated with PFS when evaluating only those patients in the DART group, where 24-month PFS was 68.4% compared to 92.6% for MRD-negative patients (HR, 0.28; 95% CI, 0.08-0.93). Three months after completion of all treatment, 8 of 117 patients (6.8%) had detectable ctHPVDNA, whereas 109 of 117 (93.2%) did not, and detection was highly associated with PFS (HR, 20.48; 95% CI, 6.91-60.67).Conclusions and RelevanceThis secondary analysis of the DART RCT found that patients with detectable ctHPVDNA after surgery had a higher risk of disease progression. When added to the pathologic factors considered, ctHPVDNA assessment may improve selection of patients for treatment de-escalation. In addition, the 3-month posttreatment time point, early in surveillance, may identify a sizable portion of patients with progression and may guide intervention and surveillance after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Trial RegistrationClinicalTrials.gov Identifier: NCT02908477

AbstractObjectiveLow‐grade parotid malignancies have high overall survival rates; however, controversy remains about the appropriate extent of surgery. We aim to explore the trends in the extent of parotidectomy performed over time in low‐grade parotid malignancies in the United States, with a hypothesis that there has been a trend towards less aggressive surgery.Study DesignRetrospective cohort study of all low‐grade (grade I) acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC) in the Surveillance, Epidemiology, and End Results (SEER) from 2004 to 2020.SettingGeographic areas served by SEER.MethodsTrends were assessed using Cochran‐Armitage tests and logistic regression; Kaplan‐Meier survival curves were used to analyze overall and cancer‐specific survival, and chi‐square tests were used to analyze patient characteristics.ResultsIn total, 1288 patients were identified (916 MEC; 372 ACC). Most patients (n = 772, 60%) were non‐Hispanic white, with an average age of 50.6 years and had a slight female predominance (1.58:1). Most of the cohort presented with tumor stage T1 or T2 (84%), N0 (90.1%), and M0 (96.9%). Treatment with total parotidectomy decreased significantly (34.6 vs 17.7%, P = .02) whereas sacrificing the facial nerve (FN) slightly decreased (20 vs 15.7%, P = .1). A significant increase in N0 patients (71%‐94%, P < .0001) was observed, whereas T staging remained stable (61%‐64%, P = .3). Overall, both ACC and MEC had excellent cancer‐specific survival.ConclusionOver the last 17 years, there has been a significant de‐escalation in the extent of parotidectomy for low‐grade parotid malignancy in the United States.

ABSTRACTBackgroundMagnetic resonance elastography (MRE) quantifies tissue viscoelasticity, offering insights into intracranial meningiomas. MRE‐derived parameters, including the storage modulus (G') and the magnitude of the complex modulus (|G*|), may aid neurosurgical planning, but their repeatability remains unexplored in brain tumors.Purpose/HypothesisTo evaluate the repeatability of G' and |G*| in meningiomas, the influence of tumor volume and spatial location on variability, and ranking stability across paired elastograms.Study TypeProspective.Population/SubjectsSeventeen paired MRE scans from 16 patients with meningiomas (mean age 64 ± 12 years, 10 females) scheduled for resection.Field Strength/SequenceMRE was performed on a 3 T system using a single‐shot spin‐echo echo‐planar imaging (SE‐EPI) sequence.AssessmentTumors were segmented on contrast‐enhanced T1‐weighted images; distance and volume metrics were extracted. Regions of interest were applied to G' and |G*| elastograms. Repeatability was evaluated using the coefficient of variation (CV%). Ranking stability was assessed by comparing median G' or |G*| values.Statistical TestsThe difference in CV% was assessed using the Wilcoxon signed rank test. Linear regression assessed the effect of tumor volume and distance from the external occipital protuberance (EOP) on CV%. The Wilcoxon signed‐rank test evaluated ranking stability and scan‐rescan CV%. Statistical significance was defined as p < 0.05.ResultsThe difference in CV% G' (14.89 ± 12.32) and CV% |G*| (13.88 ± 12.60) was not significant (p = 0.61). Tumor volume inversely correlated with CV% (G': β = −0.75 |G*|: β = −0.59). Tumor‐EOP distance had no significant effect (G': p = 0.58, |G*|: p = 0.23). Rankings remained stable (G': p = 0.82, |G*|: p = 0.71).Data ConclusionMRE‐derived parameters are repeatable in intracranial meningiomas, with G' and |G*| being equally stable. Larger tumors yielded more consistent estimates. Preserved ranking stability supports the use of MRE in preoperative planning.Evidence Level2.Technical EfficacyStage 2.

Background: Malignant mesenchymal tumors involving the parotid gland are uncommon, characteristically aggressive, and little is known with few reports documented. Study Design: Retrospective case series. Setting: Single institution tertiary care center, 2010 to 2022. Method: Patients were identified from an institutional parotid tumor database. Patient history, demographics, pathologic diagnosis, treatment, and follow up were documented. Results: Eight patients were identified, 3 were males. The average age was 61 years old, and the most common tumors identified were pleomorphic sarcomas (3 patients). Presenting symptoms included: preauricular/cheek mass in 7 patients, facial pain (4), otalgia (4), aural fullness (3), and numbness (1). All patients received a parotidectomy, and 4 patients received adjuvant therapy of either radiation or chemoradiation. Post-operatively, there were 3 cases of distant recurrence, 2 cases of regional recurrence, and 1 case of local recurrence. There were 2 reports of death. Conclusion: Malignant mesenchymal tumors of the parotid are rare, represent varied histologies. Due to their aggressive nature, surgical resection with radiation and close follow-up may be an appropriate treatment regimen in controlling the disease.

Importance Circulating tumor human papillomavirus DNA (ctHPVDNA) is an important biomarker for the presence of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but little is known about early postoperative kinetics of ctHPVDNA clearance. Objective To investigate early postoperative kinetics of ctHPVDNA in patients with HPV-associated OPSCC. Design, Setting, and Participants This prospective cohort study was conducted at a single tertiary care center from January 4, 2020, to January 26, 2023. Patients with newly diagnosed HPV-associated OPSCC undergoing surgical management were enrolled. HPV status was defined as positive if findings of p16 immunohistochemistry and/or HPV DNA in situ hybridization and/or E6/E7 RNA in situ hybridization were positive. Exclusion criteria included history of prior head and neck cancer and metastatic disease at presentation. Data were analyzed from September 1, 2024, to April 25, 2025. Exposures Transoral robotic surgery with concurrent neck dissection. Main Outcomes and Measures Blood was drawn prior to surgery (pretreatment), 1 to 2 days after surgery (postoperative days 1 to 2), and approximately 2 weeks after surgery (postoperative week 2; range, 8 to 20 days). ctHPVDNA was quantified by a tumor tissue–modified viral (TTMV) HPV DNA test. Correlations were tested between the pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels using Gaussian regression. Concordance between detectability at postoperative day 1 to 2 and postoperative week 2 was explored using negative predictive value and positive predictive value. Results Of 57 included patients with detectable pretreatment TTMV HPV DNA, 51 (89%) were male, and the median (IQR) age was 59 (54-66) years. A total of 35 patients (61%) had blood draws at all 3 time points; 16 (28%) had detectable TTMV HPV DNA on postoperative day 1 to 2. Pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels had a medium positive linear correlation ( r = 0.31; 95% CI, 0.04-0.54). Undetectable TTMV HPV DNA on postoperative day 1 to 2 blood draw had a negative predictive value of 0.95 (95% CI, 0.74-1.00) for an undetectable level on postoperative week 2 blood draw, but a detectable level on postoperative day 1 to 2 blood draw only had a positive predictive value of 0.19 (95% CI, 0.04-0.46). Of the 16 patients with detectable TTMV HPV DNA pretreatment and at postoperative day 1 to 2, only 3 (19%) continued to have detectable TTMV HPV DNA at postoperative week 2. One patient had undetectable levels at postoperative day 1 to 2 and detectable levels at postoperative week 2. Conclusions and Relevance In this study, ctHPVDNA detectability early after surgery did not predict detectability at 2 weeks after surgery. ctHPVDNA clearance early after surgery could predict a negative test at 2 weeks. A negative blood draw finding on postoperative day 1 may be used to omit a postoperative blood draw at 2 weeks for minimal residual disease detection in future clinical trials.

Abstract Objective To (1) track the incidence of pleomorphic adenomas (PAs) and (2) compare demographic and treatment trends in PAs over the last five decades in a single county. Study Design Retrospective cohort of all patients with a pathologic diagnosis of nonrecurrent PA from January 1976 to December 2022. Setting Olmsted County, Minnesota. Methods Incidence was calculated per 100,000 persons/year and age and sex‐adjusted to the US 2020 census data. Incidence trends were identified using Poisson rate regression models. Changes in clinical features of diagnosis were evaluated using Spearman rank correlation coefficient tests, Wilcoxon rank sum tests, and Kruskal‐Wallis tests. Results In total, 251 patients with PA were identified. The median age at diagnosis was 50.0 years with a slight female predominance (1.24:1). The adjusted incidence during this period is 4.79/100,000 person‐years, increasing from 2.50 in 1976 to 1979 to 5.73/100,000 persons/year in 2020 to 2022. Less extensive surgery, including partial and superficial parotidectomies, increased significantly from 1976 to 2022, whereas total parotidectomies decreased ( P < .0001). The number of patients who presented with an incidental imaging finding increased during this time period ( P < .001), as did the age at diagnosis (45‐51 years, P = .05) Conclusion The average annual incidence of PAs in Olmsted County from 1976 to 2022 is higher than reported US estimates and has increased over the last five decades. The percentage of patients who presented with incidental imaging findings increased over this period, as did the age at diagnosis. These findings highlight modern imaging techniques and an aging population more willing to seek workup and treatment of a benign parotid mass.

Objective: To assess the impact of extent of parotidectomy on surgical and oncologic outcomes in low grade mucoepidermoid carcinoma (LGMEC). Methods: A retrospective chart review of all patients undergoing primary surgical treatment for LGMEC from 2000 to 2022 was conducted. Clinical features collected included demographics, facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. Results: 58 patients were included; 10 patients underwent partial parotidectomy (PP), 38 underwent superficial parotidectomy (SP), and 10 underwent near-total/total parotidectomy. PP and SP patients had smaller tumors and more superficial tumors compared to near-total/total parotidectomy group ( P = .03). PP and SP were more likely to have negative margins and less locoregional disease compared to near-total/total parotidectomy patients ( P < .01). Near-total/total parotidectomy were more likely to undergo facial nerve resection (20% vs 0% for PP & SP respectively) ( P = .05). Immediate postoperative facial nerve function was significantly better among PP patients (73% HB I) compared to SP (44% HB I) and near-total/total parotidectomy patients (0% HB I) ( P < .01). Most patients regained their facial nerve function although only 40% of the near-total/total parotidectomy patients had a HB I at the time of last follow up ( P < .01). Patients were followed for a median of 6.2 years, during which only 1 patient (total parotidectomy) had a recurrence. Conclusions: PP offers a safe and effective approach for small LGMEC tumors, ensuring better facial nerve function postoperatively with minimal complications compared to more extensive surgery.