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AbstractBackgroundGastric cancer with synchronous peritoneal metastases is a debilitating disease with limited treatment options. This article describes an update of the 2018 Chicago Consensus guidelines addressing the management of gastric cancer with synchronous peritoneal metastases in line with the most recent evidence.MethodsA clinical management pathway was updated through two rounds of a Delphi consensus to assess agreement levels with pathway blocks. Supporting evidence underwent evaluation using a rapid literature review. Meta‐analyses were performed as appropriate.ResultsOverall, the level of evidence in this disease subset was low to moderate. Of 124 participants in the first round, 109 (88%) responded in the second round. Strong consensus (>90%) was achieved in six of eight blocks (75%) in rounds 1 and 2. A multidisciplinary preoperative assessment and diagnostic laparoscopy should be offered to all patients, whereas patients with a high burden of disease or progression should undergo nonsurgical management. Patients with stable/responsive disease and a low peritoneal carcinomatosis index should subsequently be offered treatment with regional therapeutic interventions and cytoreductive surgery. In patients who are cytology‐positive, systemic therapy can be used to convert them to cytology‐negative, with subsequent surgery offered according to the patient's goals of care. Meta‐analysis of observational and randomized control trials revealed a survival benefit with the addition of intraperitoneal chemotherapy to cytoreductive surgery (hazard ratio, 0.52).ConclusionsThe consensus‐driven clinical pathway for gastric cancer with synchronous peritoneal metastases offers vital clinical guidance for practitioners. There is a growing body of high‐quality evidence to support management strategies, and future clinical trials are eagerly awaited.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

This phase II trial of transoral surgery (TOS) with deintensified postoperative management in human papillomavirus (HPV)–associated oropharynx cancer (OPC) enrolled patients with resectable cT1-2 stage III/IV American Joint Committee on Cancer (AJCC) seventh edition p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (arm A); those with clear margins, 2-4 + LN, or ENE ≤1 mm were randomly assigned to 50 Gy (arm B) or 60 Gy (arm C); and those with involved margins, >4 + LN, or >1 mm ENE received weekly cisplatin and 60-66 Gy (arm D). Among 359 evaluable patients, the 54-month progression-free (PFS) and overall survival (OS) were 90.6% (90% CI, 87.2% to 93.1%) and 95.3% (93.0% to 96.9%), respectively. The 54-month PFS by arm was A 93.2% (79.6% to 97.8%; all four recurrences among N1 patients), B 94.9% (89.7% to 97.5%), C 90.2% (82.7% to 94.6%), and D 85.5% (77.5% to 90.8%). The 54-month OS by arm was A 97.1% (85.7% to 99.4%), B 97.9% (93.5% to 99.3%), C 95.1% (90.1% to 97.6%), and D 92.5% (86.9% to 95.7%). PFS or OS did not differ by primary site or smoking history. TOS and neck dissection with deintensified postoperative management results in outstanding 54-month PFS and OS. Among patients with favorable pathologic characteristics, those with N1 disease are at risk of late recurrence without radiation.

Background There has been growing interest in transradial procedures over the past decade due to substantial reductions in access site complications as well as improved patient recovery. While several radial-specific neurovascular catheters have come to market, all catheters that are compatible with a 7Fr sheath have small inner diameters (IDs) (0.079″–0.082″), which can limit use of modern intermediate catheters. while larger-ID catheters cannot be used with a radial sheath resulting in complications related to radial artery spasm and entrapment. We report our results using a novel 7Fr-sheath-compatible radial guide catheter with an 0.087″ ID (Piraeus 7Fr 87 NeuGlide catheter) for neurovascular procedures. Methods This is a single center retrospective case series of patients undergoing transarterial transradial neuroendovascular procedures using the Piraeus 7Fr 87 NeuGlide catheter. The primary outcome was delivery of the catheter to the target vessel and successful completion of the procedure without the need to convert to femoral access or an alternative guide. Descriptive statistics are reported. Results Forty patients were included. The most common procedure was middle meningeal artery embolization followed by aneurysm embolization. And 97.5% of procedures were completed successfully without conversion to femoral access; 75% were completed without the need of an intermediate guide catheter. One procedure required conversion to femoral access. There were no access site or neurological complications. Conclusion The Piraeus 7Fr 87 NeuGlide catheter is both safe and effective for neurovascular procedures. The larger ID and 7Fr compatible outer diameter allows for the use of standard 5Fr and 6Fr intermediate/aspiration catheters.

OBJECTIVE The principal tenet of minimally invasive neurosurgery is to limit approach-related tissue trauma, and a major assumption is that shorter incisions and smaller openings, in addition to protecting the brain, also have some perceptible benefits for the patient. This study tests the assumption of patient benefit and tries to define its significance. METHODS Procedures that fit the inclusion criteria of minimally invasive transcranial "keyhole" surgery were sought in the principal investigator’s archives. Each case was then paired with a classic procedure performed within the study time frame by the two senior authors, matched for pathology, size, location, and complexity. These pairs were then compared using a statistical tool (i.e., the Wilcoxon signed-rank test) designed for matched samples. Differences in estimated blood loss, duration of surgery, and length of hospital stay were examined. The narcotic needs during hospitalization were also examined as morphine milligram equivalent (MME). RESULTS Ninety patients were included in this study, evenly split between the minimally invasive surgery (MIS) and classic cohorts. Comparison of the 45 pairs showed no significant difference in estimated blood loss, though the operative times favored the MIS cohort significantly (mean ± SEM 310 ± 17 minutes vs 383 ± 24 minutes, p = 0.02). The length of stay was shorter for MIS, but the difference reached statistical significance only when cases with complications were excluded. The most important finding was that significantly less narcotic was needed during hospitalization in the MIS cohort (83 ± 15 MME vs 257 ± 47 MME). CONCLUSIONS The large difference in narcotic needs points to enhanced recovery from MIS techniques. While the difference in operative time did not lead to significantly shorter hospital stays, data suggest that minimally invasive technique may benefit the patient during recovery. This inspires further investigations to define the potentially positive impact on hospital and healthcare systems.

ABSTRACT Background Sulfa antibiotic allergy labels (SALs) are encountered frequently in kidney transplant recipients (KTs). This often results in patients receiving second‐line prophylaxis for both Pneumocystis jiroveci and urinary tract infections (UTIs). The effect of SAL on outcomes including UTIs after KT is unclear. Methods In our single‐center retrospective cohort study, we investigated the effect of SALs on bacteriuria after KT. We identified patients with pre‐KT SALs from 2011 to 2022. A matched cohort was then created using KT with no pretransplant SALs. The groups were compared using proportional analysis and univariable and multivariable Cox proportional regression models. The primary outcome of interest was the proportion of individuals experiencing one or more episodes of bacteriuria within 1 year posttransplant. Secondary outcomes included bacteremic UTIs, acute kidney injury, and opportunistic infections. Results We found that the proportion of individuals experiencing bacteriuria within the first‐year posttransplant was significantly greater in the SAL group versus the control group ( n = 21, 28% vs. n = 22, 14.7%, p = 0.012). This result was also seen in univariable and multivariable survival analysis. In addition, episodes of UTI with associated bacteremia ( n = 11, 14.7% vs. n = 5, 3.3%, p = 0.002) were statistically significantly higher in the SAL group. Conclusion There was a significantly greater number of episodes of bacteriuria in the first‐year posttransplant in subjects with pretransplant SAL. Based on our findings, we suggest that all KTs with pretransplant SALs undergo evaluation and intervention prior to transplantation. image

e18031 Background: HPV+ OPSCC has better outcomes than HPV negative OPSCC but more distant metastatic potential. ICM in HPV+ OPSCC are rare. Data regarding risk factors, clinical presentation and outcomes after ICM diagnosis is limited. This study describes clinical characteristics and outcomes of patients (pts) with HPV+ OPSCC who develop ICM. Methods: Retrospective analysis of pts with HPV+ OPSCC and ICM between 2010 - 2024. Demographic, clinicopathologic, and survival data was collected. Skull base recurrences were excluded. Univariate and multivariate analyses used Cox proportional hazard models; continuous variables binarized by receiver operator curves. Survival assessed via Kaplan-Meier method; reported as median (95% CI). Calculations use BlueSky (v10.3.1). Results: Among 1,999 pts with HPV+ OPSCC, 16 (0.8%) had ICM. Pt characteristics and treatment are summarized in Table 1. Primary tumor sites were base of tongue (56%), tonsil (38%), and unknown (13%). Most pts (n=8, 50%) presented with stage IV disease (6 extracranial metastasis (ECM), 1 ICM only, 1 both). Frontal and parietal lobes were the most frequent ICM sites. Neurological symptoms were present in 10 (62%) pts; ICM was incidentally found in 6 (38%) pts. Median overall survival (mOS) from initial diagnosis was 34 months (21 – not reached) and median time from diagnosis to ICM was 24 months (range 1-112). mOS following ICM detection was 10.9 months (4 -18). On multivariate analysis, only surgical resection (hazard ratio [HR] 0.03, p<0.01) and radiotherapy (HR 0.01, p<0.02) were independently associated with post-ICM survival. With median follow up of 100 months, 14 pts (88%) had died; 2 (12%) were alive. Conclusions: ICM from HPV+ OPSCC are rare but devastating with a mOS <1 year from detection. Most pts were symptomatic, had de novo metastatic disease, and had other sites of metastases. Surgical resection and radiation were associated with improved OS. Multicenter efforts to investigate predictors, multiomic sequencing and identification of pt subsets who may benefit from ICM screening are warranted. Baseline characteristics of Pts with ICM in HPV+ OPSCC. Variable Summary statistics (n=16) Median age (range) 58 (34-71) Male 14 (88%) Smoking history 10 (60%) Clinical stage at diagnosis Stage I: 4 (25%) Stage II: 2 (12.5%) Stage III: 2 (12.5%) Stage IV: 8 (50%) Symptoms at ICM diagnosis Incidental: 6 (38%)Neurological: 10 (62%) Seizure (n=3) Motor/Sensory symptoms (n=3) Altered mental status (n=2) Cognitive symptoms (n=1) Dizziness (n=1) ICM site Frontal lobe: 7 (44%) Parietal lobe: 7 (44%) Occipital lobe: 4 (25%) Temporal lobe: 2 (13%) Cerebellum: 2 (13%) Concurrent ECM Bone: 11 (69%) Lung: 9 (56%) Lymph node: 6 (38%) Liver: 5 (31%) Kidney: 1 (6%) Cranial nerve: 1 (6%) Treatment after ICM Radiotherapy: 15 (94%) Chemotherapy: 10 (63%) Immunotherapy: 9 (56%) Surgery: 8 (50%)

6106 Background: Treatment options for pts with R/M SGC are limited. Responses to chemotherapy (CT) are low with high toxicity and responses to immune checkpoint inhibition (ICI) are <10%. Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. 1 Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with non-adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735). Pts were treated in 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease, and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR). Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 25 pts were enrolled Aug 2021-Feb 2024; 1 cancelled prior to treatment. Of 24 eligible and treated pts, median age was 59.5 years (46-77), 66.7% male, performance status 0 (62.5%) or 1 (37.5%). Histologies were salivary duct carcinoma (SDC, 11), acinic cell carcinoma (8), mucoepidermoid carcinoma (MEC, 3), myoepithelial carcinoma (1), and carcinoma NOS (1). 7 pts had no prior therapies (29.2%). The remaining pts had 1 (33.3%), 2 (29.2%), or ≥ 3 lines of therapy (8.3%). 83.3% of pts had no prior ICI. Median cycles of treatment was 8 (2-34), and duration of response was 12.5 months (4.1-20.6). 9 of 24 pts had a confirmed partial response (PR) for ORR of 37.5% (CI: 18.8-59.4). PRs were seen in 7 pts with SDC (7 of 11, 63.6% PR), 1 with MEC, and 1 with acinic cell. Stable disease (SD) was seen in 5 (20.8%), progressive disease in 8 (33.3%), and 2 didn’t have post-baseline imaging, but were considered non-responders per protocol. Clinical benefit rate was 58.3% (CI: 36.6-77.9). With median follow-up of 12.0 months (2-34.7), median OS is 20.7 months (CI: 17.3-not reached) and median PFS is 6.2 months (CI: 2.1-17.3). 1-year OS and PFS rate is 76.3% (95% CI: 59.9-97.2) and 36.1% (CI: 21.01-62.2), respectively. Common toxicities were grade 1 fatigue and nausea. 6 pts (25.0%) had ≥1 grade 3-4 toxicity possibly related to treatment, mostly hematologic. The 4 pts with grade 3-4 non-heme toxicity had grade 3 fatigue, rash, and heart failure, and 1 grade 4 hypokalemia. Correlative studies investigating biomarkers of response are underway. Conclusions: PTX and PMB has activity in pts with R/M SGC, with promising responses in pts with SDC and median response duration of 1 year. 1 Viscuse et al. Head Neck 2019;41(6):E99-103. Clinical trial information: NCT04895735 .

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 .