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3069 Background: Molecular targeted agents have revolutionized cancer diagnosis and treatment. Intraoperative molecular imaging (IMI) is a novel technique that entails performing real-time, in vivo optical imaging during surgery to ensure cancer clearance. A multicenter clinical trial was conducted using abenacianine, a cathepsin targeted near-infrared (NIR) IMI agent to visualize pulmonary nodules during surgery. The primary objective was to assess the efficacy of abenacianine in localizing pulmonary lesions, evaluating surgical margin, and identifying unsuspected disease. Methods: Participants scheduled to undergo surgery for known or suspected cancer in the lung received abenacianine (0.32 mg/kg intravenous) preoperatively 12 to 36 hours before surgery. During a standard-of-care surgery, the lung underwent IMI and additional disease not identified by conventional methods were identified and analyzed. Efficacy was measured by frequency of clinically significant events (CSEs) defined as localization of lesions not found by standard surgical techniques, identification of additional cancers, identification of positive surgical margins confirmed by histology, and detection of cancerous lymph nodes. Results: 89 participants were included in the study. The mean age was 67 years and 57 (64%) were female. Of 89 participants administered abenacianine who underwent standard of care surgical resection for known or suspected cancer in the lung, 40 (45%) had at least one CSE. Abenacianine with NIR imaging identified lesions that were not found by standard surgical methods in 34 (38%) participants, synchronous and occult cancers that were not found by pre-operative imaging in 2 (2%), margins within 10 mm of the closest staple line in 8 (9%), and lymph nodes determined to be cancerous in 1 (1%) participant. Tumors visualized by IMI with abenacianine included non-small cell lung cancers (adenocarcinoma, squamous cell carcinoma, neuroendocrine tumor) and cancers that metastasized to the lung (breast, colorectal, prostate, thymoma, renal cell, sarcoma). Abenacianine was safe and well tolerated in this study; there were no drug-related serious adverse events. Conclusions: This Phase 2 multicenter study demonstrated that using IMI with abenacianine during standard-of-care lung cancer surgery markedly improved clinical outcomes. Abenacianine localized tumors intraoperatively, identified synchronous and occult lesions, helped assess negative margin status, and identified cancerous lymph nodes enabling a more complete oncologic resection. Clinical trial information: NCT06145048 .

e16157 Background: The optimal treatment for resectable gastric/GEJ AC is unclear due to limited direct comparisons among chemotherapy and chemoradiation regimens. Addressing this gap is critical to improve patient outcomes. We performed this network meta-analysis (NMA) to determine the relative efficacy of multimodality regimens for resectable gastric/GEJ AC. Methods: MEDLINE, EMBASE, Scopus, and CENTRAL were searched from inception till September 20, 2024, to identify phase III trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ AC. Primary outcomes were disease-free survival (DFS) and overall survival (OS). A frequentist NMA was conducted to compare hazard ratios (HR) and 95% CI for each outcome. Relative treatment rankings were assessed using P-scores. Results: Fifteen trials (8,072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P score 91%) (Table), significantly outperforming surgery alone (HR 0.48, 95% CI 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF+nCRT(EP) (neoadjuvant cisplatin, leucovorin and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P score 90%) and pFLOT (P score 87%) were the top regimens, with pFLOT significantly outperforming surgery alone (0.57, 0.45-0.72), and nCROSS (0.73, 0.60-0.89). Adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (CF/CX) (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT in terms of DFS (1.10, 0.71-1.69) or OS (1.09, 0.69-1.72). Conclusions: pFLOT demonstrated superior efficacy in resectable gastric/GEJ AC, surpassing surgery alone, nCROSS, and other perioperative regimens. The additive role of immunotherapy to pFLOT requires further investigation to refine patient selection and optimize outcomes. Regimen Overall Population GEJ cohort OS DFS OS DFS nPLF+nCRT(EP) 1 (90) 2 (84) 1 (85) NA pFLOT 2 (87) 1 (91) 2 (79) 2 (88) pPembrolizumab+CF/CX 3 (75) 3 (81) 5 (41) - nECX 4 (61) 5 (55) - - pCF 5 (59) 8 (51) 3 (72) - pECF/ECX 6 (47) 6 (55) 7 (40) 3 (57) nECX+aCRT(CX) 7 (45) 7 (52) 9 (31) - nCF 8 (42) 10 (28) 6 (40) - nCROSS 9 (41) 9 (35) 8 (34) 4 (43) pECF/ECX/FLOT+nCRT(F/X) 10 (38) 4 (57) 4 (72) 1 (90) nCRT(CF) 11 (9) 11 (6) - 5 (14) Surgery 12 (7) 12 (5) 10 (5) 6 (9) Data reported as rank (P-score). Abbreviations: n: neoadjuvant; p: perioperative; ECX: epirubicin + cisplatin + capecitabine; CF: cisplatin + fluorouracil; ECF: epirubicin + cisplatin + fluorouracil; aCRT(CX): adjuvant radiotherapy + cisplatin + capecitabine; CRT(F/X): fluorouracil/capecitabine + radiotherapy; CRT(CF): cisplatin + fluorouracil + radiotherapy.

501 Background: EA1181 (NCT04266249) is a single-arm trial of neoadjuvant THP for patients with clinical anatomic stage II/III HER2+ breast cancer; patients with cT4 or cN3 disease were excluded . Assessing the primary endpoint, 3-year recurrence-free survival in patients with a pCR (ypT0/Tis, ypN0), requires longer follow-up. Here, we present results for the secondary objective of pCR rate and its relation to clinicopathologic factors and the HER2DX pCR likelihood score (Reveal Genomics) derived from gene expression and clinical features. Methods: Patients received 4 cycles of trastuzumab and pertuzumab (HP) with weekly paclitaxel (12 weeks) or docetaxel (q3w x 4), followed by surgery. Clinicopathologic features were assessed for all patients and HER2DX pCR score (stratified by ER status) was determined using the diagnostic biopsy in a representative subset of study participants. Results: 2175 patients were enrolled. Median age was 55 years (range 22-88 years); 58% had clinical stage IIA, 33% stage IIB, and 9% stage III. 45% had nodal involvement (mostly cN1). 781 tumors were HER2+/ER- and 1394 HER2+/ER+ (locally tested ). 2141 patients started THP, for whom the pCR rate was 44% overall, 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Disease progressed during THP in 16 patients (0.7%). The pCR rate varied inversely to the proportion of cells staining for ER among patients with HER2+/ER+ breast cancer: 1-10%+, 62.5%; 11-69%, 51.6%; ≥70%, 22.5% (p <0.001). The pCR rate was significantly associated with higher grade, especially in HER2+/ER+ disease. T and N stage did not significantly affect pCR rate. Among 569 patients assessed for the HER2DX pCR score, the pCR rate was significantly greater for patients with a higher vs lower score, regardless of ER status (Table). Further correlations and interactions will be presented. Conclusions: Neoadjuvant THP resulted in pCR in nearly two-thirds of pts with clinical stage II/III HER2+/ER- and in one-third with HER2+/ER+ breast cancer. There was no association with clinical stage. Lower ER expression and higher grade were associated with higher pCR rates. The HER2DX pCR score was a significant predictor of pCR, regardless of ER status. Clinical trial information: NCT04266249 . All Participants HER2+/ER- HER2+/ER+ # patients enrolled pCR rate (95% CI) # patients enrolled pCR rate (95% CI) # patients enrolled pCR rate (95% CI) Evaluable Cohort 2141 44%(42-46%) 774 64%(60-67%) 1367 32%(30-35%) HER2DX Cohort 569 48%(44- 52%) 230 69% (63-75%) 339 34%(29-39%) HER2DX pCR-high score 182 (32%) 68%(60-74%) 147 (64%) 70% (62-77%) 36 (11%) 58%(41-74%) HER2DX pCR-medium score 161 (28%) 67% (59- 74%) 70 (30%) 74%(62- 84%) 89 (26%) 61%(50-71%) HER2DX pCR-low score 226 (40%) 19%(14- 25%) 13 (6%) 31%(9-61%) 214 (63%) 18%(13-24%) P-value HER2DX score <0.001 0.010 <0.001

Low-grade endometrial stromal sarcomas (LG-ESS) are the second most common malignant uterine mesenchymal tumors, but in contrast to the more common leiomyosarcomas, they are often characterized by a prolonged and relatively indolent course. However, a subset of patients experience significant morbidity or die of disease, and it is difficult to predict which tumors will behave aggressively, with most published studies limited in either the number of tumors or the depth of pathologic parameters evaluated. Thus, we studied the clinicopathologic features of LG-ESS in 102 patients ranging from 21 to 74 (median: 47) years. All were treated with hysterectomy and staged according to both the FIGO 2018 system (stage IA=22, IB=36, I-not otherwise specified=5, II=16, III=13, IV=10) and the FIGO 1988 system (stage I=62, II=1, III=17, IV=22). Tumors measured 1.2-49 (median: 7) cm. Microscopically, 69 involved the endometrium while 33 were centered in the myometrium. Thirteen showed only minimal infiltration of the myometrium while the rest displayed the typical extensive myometrial permeation. The cervical stroma was involved in 18, the uterine serosa in 27, and the parametrium in 22. Conventional morphology resembling proliferative endometrial stroma was seen in 95, fibroblastic appearance in 35, smooth muscle differentiation in 23, sex cord-like differentiation in 21, stromal hyalinization in 21, and myxoid stroma in 9. Less common features included glandular differentiation resembling adenomyosis (n=5), pseudopapillary pattern (n=1), deciduoid appearance (n=2), adipocytic differentiation (n=2), multinucleated cells (n=2), and rhabdomyoblastic differentiation (n=1). Mitoses ranged from <1 to 20 per 10 high-power fields (median=3). Lymphovascular invasion and infarct-type necrosis were present in 64 and 23, respectively. Follow-up was available in all patients ranging from 16 to 358 (median: 79) months. Forty-six received adjuvant treatment as hormonal therapy (n=34), radiation (n=4), radiation and hormonal therapy (n=4), chemotherapy (n=3), or chemotherapy and radiation (n=1). Three patients had persistent unresected tumor following surgery, and an additional 34 had recurrences at intervals of 3 to 272 (median: 79) months, including 2 tumors with minimal infiltration. At last follow-up, 75 patients were alive with no evidence of disease, 14 were alive with disease, and 9 died of disease at intervals of 16 to 167 (median=70) months. Four died of unrelated causes without recurrence. Five-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 80% and 94%, while 10-year RFS and DSS were 51% and 87%, respectively. On statistical analysis, cervical stromal involvement ( P =0.018) and myxoid stroma ( P <0.001) were associated with shorter recurrence-free survival. Tumors lacking a conventional component had worse disease-specific survival ( P =0.048). All other clinical and morphologic features, including stage, were not significantly associated with outcome. On multivariate analysis, only cervical stromal involvement remained an independent predictor of recurrence-free survival ( P =0.047; HR: 16.939) and no factors were independently predictive of disease-specific survival. Our findings highlight the difficulty in predicting outcomes in these tumors, likely due to slow progression and frequent treatment responses even in the recurrent setting. We confirm the potential for recurrence even in tumors initially showing minimal infiltration. Cervical stromal involvement and lack of conventional morphology are potential novel risk factors that should be further evaluated in subsequent studies.

Abstract Background Optimal treatment for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma remains unclear due to limited head-to-head comparisons among chemotherapy and chemoradiation regimens. This network meta-analysis aimed to determine the relative efficacy of available multimodality treatment regimens in these patients. Methods MEDLINE, EMBASE, Scopus, Web of Science, and CENTRAL were searched till September 20, 2024. Phase 3 randomized trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ adenocarcinoma were included. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Frequentist network meta-analysis was conducted to compare hazard ratios (HRs) and 95% confidence intervals (CIs). Results Fifteen trials (8072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P-score 91%), achieving significant improvements compared to surgery alone (HR 0.48, 95% CI, 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin, and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF + nCRT(EP) (neoadjuvant cisplatin, leucovorin, and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P-score 90%) and pFLOT (P-score 87%) were the top regimens. pFLOT significantly outperformed surgery alone (0.57, 0.45-0.72) and nCROSS (0.73, 0.60-0.89). Based on the limited data available, adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT (DFS: 1.10, 0.71-1.69; OS: 1.09, 0.69-1.72). Conclusions pFLOT demonstrated superior efficacy in resectable gastric/GEJ adenocarcinoma, outperforming surgery alone, nCROSS, and alternative perioperative regimens. The additive role of immunotherapy requires further investigation to optimize patient selection and outcomes.

Managing persistent atrial fibrillation (AF) remains challenging due to its complex arrhythmic substrate, and pulmonary vein isolation through catheter ablation remains the primary treatment. This meta-analysis aims to compare the efficacy and safety outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in patients with persistent AF to provide evidence-based insights for clinical decision-making. A systematic search of PubMed, Embase, and Cochrane Central was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) comparing CBA and RFA in persistent AF were included. Data on efficacy, safety, and procedural outcomes were pooled in the form of odds ratios (ORs) or mean differences (MDs) with corresponding 95% confidence intervals (CIs) using the random effects model in the Review Manager (RevMan) software. Four RCTs comprising 899 patients were included in our analysis. There were no significant differences between CBA and RFA in terms of AF recurrence, atrial tachycardia/flutter recurrence, or any arrhythmia recurrence during a mean follow-up period of 18 months after ablation. Procedure time was significantly shorter with CBA (MD: −44.85 minutes, 95% CI: −56.46 to −32.24, P < 0.01), while fluoroscopy time was comparable between the 2 groups (MD: 4.31 minutes, 95% CI: −1.79 to 10.40, P = 0.17). Safety outcomes, including overall complications, phrenic nerve palsy, access-site complications, and pericardial effusion, showed no significant differences between the 2 groups. CBA and RFA show similar rates of atrial arrhythmia recurrence and periprocedural complications in the treatment of persistent AF, while CBA offers the advantage of a shorter procedure time.

AbstractAimThere is increasing adoption of nonoperative management of rectal cancer; however, the extent to which trainees are proficient in nonoperative management is unclear. The aim of this work was to describe the exposure of recent colorectal resident graduates to nonoperative management, their comfort level in assessing clinical responses and their comfort in performing rectal cancer surgeries.MethodThis was an online survey of Accreditation Council for Graduate Medical Education‐certified colorectal surgery residency graduates of training programmes in 2020, 2021 and 2022 utilizing their respective WhatsApp class chat groups. Data on resident comfort in assessing complete or near complete clinical response as part of nonoperative management, adoption in practice and perceived effects on rectal cancer operative experience were collected.ResultsForty five graduates responded, with 83.3% exposed to nonoperative management in training. Eighty five per cent utilize nonoperative management in their own practices and 37.1% felt it had a negative impact on preparing them for rectal cancer surgeries. While 82.4% felt comfortable assessing a complete clinical response, only 61.8% felt comfortable assessing a near complete response. Residents who perceived a positive effect on their training felt more comfortable assessing a complete or near complete response.ConclusionMost recent graduates were exposed to nonoperative management in training and utilize it in practice, although many did not feel comfortable assessing a near complete response. A significant portion felt it had a negative impact on their experience and quantity of rectal cancer surgeries. This suggests a need to improve colorectal resident education in nonoperative management of rectal cancer while simultaneously preserving surgical experience for trainees.

Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.

Atopic dermatitis affects 20% to 25% of children and has significant impact on quality of life of patients and families. Recent studies of the pathogenesis of AD highlight the interplay between a defective skin barrier, immune dysfunction, and the cutaneous microbiome. Standard of care for AD treatment includes topical corticosteroids for active disease and moisturization to repair the barrier defect. Emerging treatments include dupilumab and Janus kinase (JAK) inhibitors. Reduction of triggers and proactive treatment with topical corticosteroids and/or topical calcineurin inhibitors can reduce flares. Treatment plans should be clear and as simple as possible to maximize adherence.

This study reveals how EEG burst activity changes with progressive hypoxia, offering insights into its neural correlates. Increased burst features in specific frequency bands correlate strongly with physiological, such as decreasing peripheral oxygen, task performance, such as declining accuracy, and symptom measures, such as increasing report rate. Our findings characterize a neural signature with potential use for real-time EEG monitoring to enhance hypoxia detection in aviation, potentially improving flight safety.