Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer.

OBJECTIVE: In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Circulating tumor DNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear. METHODS: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor agnostic NGS utilizing the Tempus x|F 105 gene panel at three timepoints: pre-therapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9, and the prognostic significance of ctDNA detection were analyzed. RESULTS: 56 patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs. 30.0, P=0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 U/mL vs. 31.5 U/mL; P=0.01), while those with ctDNA present at diagnosis did not (198.1 U/mL vs. 113.8 U/mL; P=0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free-survival. CONCLUSION: This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.

Utilization and survival outcomes of neoadjuvant chemotherapy for early-stage gastric cancer.

BACKGROUND AND OBJECTIVES: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers. METHODS: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS). RESULTS: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34). CONCLUSIONS: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes.

The differential effect of neoadjuvant chemotherapy and chemoradiation on nodal downstaging in pancreatic adenocarcinoma.

BACKGROUND/OBJECTIVES: Neoadjuvant chemotherapy (NCT) and chemoradiotherapy (NCRT) enhance resectability in patients with pancreatic adenocarcinoma (PDAC). This study compares the effect of NCT and NCRT on lymph nodal downstaging and survival. METHODS: The 2004-2016 National Cancer Database Pancreas Participant User File was used to identify patients who underwent surgery for PDAC. Fisher's exact, Wilcoxon rank-sum, multivariate logistic regression, and log-rank were used. Downstaging was defined as clinically node-positive patients who demonstrated node-negativity on pathology. RESULTS: Of 42,545 patients meeting criteria, 3311 received NCT and 1511 received NCRT. After surgery for clinically node-positive disease, 23.3% of NCT patients and 41.3% of NCRT patients demonstrated nodal downstaging. Younger age and lower tumor grade independently predicted downstaging. Downstaging after neoadjuvant therapy was associated with improved survival versus no nodal treatment response (29.8 vs. 22.8 months, p < 0.001). Downstaging by NCT was associated with improved overall survival versus downstaging by NCRT (37.5 vs. 26.6 months, p = 0.001). No survival difference existed between those with no nodal response after NCT or NCRT (p = 0.101). CONCLUSIONS: Although nodal downstaging is more likely post-NCRT, survival is superior in those downstaged post-NCT. Overall survival is determined by the systemic burden of disease. Post-therapy histologic analysis may be less prognostic post-NCRT.

Weight loss during neoadjuvant chemotherapy impacts perioperative outcomes in patients undergoing surgery for pancreatic cancer.

BACKGROUND: While use of neoadjuvant chemotherapy (NAC) in pancreatic adenocarcinoma (PDAC) downstages cancers to be eligible for resection, weight loss during the neoadjuvant period due to cancer progression, gastric outlet obstruction, or neoadjuvant therapy itself is an area of concern. The goal of this study is to determine the effect of weight loss during NAC on perioperative outcomes of pancreatectomies. METHODS: The NSQIP database 2014-2019 was utilized to study patients who received NAC for PDAC and underwent significant weight loss, defined as at least 10 % body weight loss in the six months prior to surgery. Univariate and multivariate analyses were conducted using Fisher's Exact Test, Pearson's Chi-squared Test, and logistic regression. RESULTS: Of the 5590 PDAC patients who received NAC, 913 (16%) experienced significant weight loss. Patients who experienced significant weight loss were more likely to experience at least one complication compared to those who did not undergo weight loss (42.2% vs. 38.7%, p = 0.023). Those who had significant weight loss were more likely to undergo unplanned intubation postoperatively (3.8% vs 2.2 %, p = 0.004), have postoperative ventilator need >48 h (3.7% vs 1.8%, p < 0.001), have postoperative septic shock (3.9% vs 1.8 %, p < 0.001), and undergo reoperation (6.0% vs 4.3%, p = 0.027). However, there were no differences for pancreatic fistula (7.7% vs 9.3 %, p = 0.15), readmission rates (15% vs 15 %, p = 0.7), or 30-day mortality (1.5% vs 1.2%, p = 0.5). Utilizing logistic regression, BMI (OR: 1.05, p = 0.032), significant weight loss (OR = 1.18, p = 0.025), sex (OR = 1.26 with female baseline, p < 0.001), history of COPD (OR = 1.39, p = 0.012), hypertensive medication use (OR = 1.18, p = 0.004), and pancreatic radiotherapy (OR = 1.16, p = 0.010) were independent preoperative predictors of a post-operative complication. CONCLUSIONS: Nutritional measures to stabilize weight during NAC should be considered to decrease post-pancreatectomy complications.

The inaccuracies of gastric adenocarcinoma clinical staging and its predictive factors.

INTRODUCTION: Accurate clinical staging (CS) of gastric adenocarcinoma is important to guide treatment planning. Our objectives were to (1) assess clinical to pathologic stage migration patterns for patients with gastric adenocarcinoma, (2) identify factors associated with inaccurate CS, and (3) evaluate the association of understaging with survival. METHODS: The National Cancer Database was queried for patients who underwent upfront resection for stage I-III gastric adenocarcinoma. Multivariable logistic regression was used to detect factors associated with inaccurate understaging. Kaplan-Meier analyses and cox proportional hazards regression were performed to assess overall survival (OS) for patients with inaccurate CS. RESULTS: Of 14 425 analyzed patients, 5781 (40.1%) patients were inaccurately staged. Factors associated with understaging included treatment at a Comprehensive Community Cancer Program, presence of lymphovascular invasion, moderate to poor differentiation, large tumor size, and T2 disease. Based on overall CS, median OS was 51.0 months for accurately staged patients and 29.5 months for understaged patients (<0.001). CONCLUSION: Clinical T-category, large tumor size, and worse histologic features lead to inaccurate CS for gastric adenocarcinoma, impacting OS. Improvements to staging parameters and diagnostic modalities focusing on these factors may improve prognostication.

Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder.

BACKGROUND: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the 'gender paradox' and 'delayed-onset pathway' hypotheses of female CD. METHODS: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9-18 years), compared to 864 sex- and age-matched typically developing controls. RESULTS: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the 'gender paradox' hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the 'delayed-onset pathway' hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. CONCLUSIONS: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the 'gender paradox' and 'delayed-onset pathway' hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes.

Can facial emotion recognition be rapidly improved in children with disruptive behavior? A targeted and preventative early intervention study.

An impairment in recognizing distress is implicated in the development and severity of antisocial behavior. It has been hypothesized that a lack of attention to the eyes plays a role, but supporting evidence is limited. We developed a computerized training to improve emotion recognition in children and examined the role of eye gaze before and after training. Children referred into an intervention program to prevent antisocial outcomes completed an emotion recognition task with concurrent eye tracking. Those with emotion recognition impairments (n = 54, mean age: 8.72 years, 78% male) completed the training, while others (n = 38, mean age: 8.95 years, 84% male) continued with their usual interventions. Emotion recognition and eye gaze were reassessed in all children 8 weeks later. Impaired negative emotion recognition was significantly related to severity of behavioral problems at pretest. Children who completed the training significantly improved in emotion recognition; eye gaze did not contribute to impairment or improvement in emotion recognition. This study confirms the role of emotion recognition in severity of disruptive behavior and shows that a targeted intervention can quickly improve emotion impairments. The training works by improving children's ability to appraise emotional stimuli rather than by influencing their visual attention.

Artificial intelligence in dermatopathology: Diagnosis, education, and research.

Artificial intelligence (AI) utilizes computer algorithms to carry out tasks with human-like intelligence. Convolutional neural networks, a type of deep learning AI, can classify basal cell carcinoma, seborrheic keratosis, and conventional nevi, highlighting the potential for deep learning algorithms to improve diagnostic workflow in dermatopathology of highly routine diagnoses. Additionally, convolutional neural networks can support the diagnosis of melanoma and may help predict disease outcomes. Capabilities of machine learning in dermatopathology can extend beyond clinical diagnosis to education and research. Intelligent tutoring systems can teach visual diagnoses in inflammatory dermatoses, with measurable cognitive effects on learners. Natural language interfaces can instruct dermatopathology trainees to produce diagnostic reports that capture relevant detail for diagnosis in compliance with guidelines. Furthermore, deep learning can power computation- and population-based research. However, there are many limitations of deep learning that need to be addressed before broad incorporation into clinical practice. The current potential of AI in dermatopathology is to supplement diagnosis, and dermatopathologist guidance is essential for the development of useful deep learning algorithms. Herein, the recent progress of AI in dermatopathology is reviewed with emphasis on how deep learning can influence diagnosis, education, and research.

Erythema ab igne with features resembling keratosis lichenoides chronica.

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.

Improving emotion recognition is associated with subsequent mental health and well-being in children with severe behavioural problems.

Impaired emotion recognition is a transdiagnostic risk factor for a range of psychiatric disorders. It has been argued that improving emotion recognition may lead to improvements in behaviour and mental health, but supportive evidence is limited. We assessed emotion recognition and mental health following a brief and targeted computerised emotion recognition training in children referred into an intervention program because of severe family adversity and behavioural problems (n = 62; aged 7-10). While all children continued to receive their usual interventions, only children impaired in emotion recognition (n = 40) received the emotion training. Teachers blind to whether or not children had received the training rated children's mental health problems before and 6 months after the training. Participants who received the emotion training significantly improved their recognition of negative and neutral facial expressions. Although both groups showed improved behaviour at follow-up, the reduction in behavioural problems was only significant in children who received the emotion training. Post-training emotion recognition scores predicted mental health problems 6 months later independently of initial emotion recognition ability and severity of behavioural problems. The results are consistent with the view that targeting emotion recognition can improve longer term functioning in individuals with disruptive behaviour, although further research using fully randomised designs is needed before causal conclusions can be drawn with confidence.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Intralesional immunotherapy for molluscum contagiosum: A review.

Molluscum contagiosum (MC) is a common cutaneous viral infection with no standard treatment. The virus responsible for MC is thought to be cleared by cell mediated immunity (CMI). Intralesional immunotherapy that stimulates CMI has been shown to be an effective treatment for other cutaneous viruses. In this review, we evaluate the efficacy and safety of intralesional immunotherapy in the treatment of MC. Articles met inclusion criteria if they examined the effects of intralesional immunotherapy as a treatment for MC, with a clear outcome and reproducible methodology. 228 studies were screened and 10 studies met criteria for inclusion. Intralesional immunotherapies investigated included candida, combined measles, mumps, rubella vaccine, tuberculin purified protein derivative, vitamin D3, interferon α, and Streptococcal substrain OK-432. Studies demonstrated clearance of MC lesions following intralesional immunotherapy, with complete response rates between 36% and 100%. No serious adverse effects were noted. Intralesional immunotherapy is a safe and effective treatment option for MC in pediatric and adult patients.

The nature and extent of emotion recognition and empathy impairments in children showing disruptive behaviour referred into a crime prevention programme.

Childhood disruptive behaviour has been linked to later antisocial and criminal behaviour. Emotion recognition and empathy impairments, thought to be caused by inattention to the eye region, are hypothesised to contribute to antisocial and criminal behaviour. This is the first study to simultaneously examine emotion recognition and empathy impairments, their relationship, and the mechanism behind these impairments, in children with disruptive behaviour. We hypothesised that children with disruptive behaviour would exhibit negative emotion recognition and cognitive and affective empathy impairments, but that these impairments would not be due to reduced attention to the eye region. We expected these emotion impairments to be driven by disruptive behaviour. We also expected a relationship between emotion recognition and cognitive empathy only. Ninety-two children with disruptive behaviour, who were participating in a police crime prevention programme and rated by their schoolteacher using the Strengths and Difficulties Questionnaire (DB; mean age 8.8 years, 80% male), took part. There was a comparison group of 58 typically developing children (TD; mean age 9.7 years, 78% male). All children completed emotion recognition and empathy tasks, both with concurrent eye tracking to assess social attention. Not only were DB children significantly impaired in negative emotion and neutral emotion recognition, and in cognitive and affective empathy compared to the TD children, but severity of disruptive behaviour also predicted intensity of emotion impairments. There were no differences in social attention to the eye region. Negative emotion recognition and empathy impairments are already present in an identifiable group of children displaying disruptive behaviour. These findings provide evidence to encourage the use of targeted interventions.

Accuracy of Capillary and Arterial Whole Blood Glucose Measurements Using a Glucose Meter in Patients under General Anesthesia in the Operating Room.

BACKGROUND: The aim of this study was to evaluate the use of a glucose meter with surgical patients under general anesthesia in the operating room. METHODS: Glucose measurements were performed intraoperatively on 368 paired capillary and arterial whole blood samples using a Nova StatStrip (Nova Biomedical, USA) glucose meter and compared with 368 reference arterial whole blood glucose measurements by blood gas analyzer in 196 patients. Primary outcomes were median bias (meter minus reference), percentage of glucose meter samples meeting accuracy criteria for subcutaneous insulin dosing as defined by Parkes error grid analysis for type 1 diabetes mellitus, and accuracy criteria for intravenous insulin infusion as defined by Clinical and Laboratory Standards Institute guidelines. Time under anesthesia, patient position, diabetes status, and other variables were studied to determine whether any affected glucose meter bias. RESULTS: Median bias (interquartile range) was -4 mg/dl (-9 to 0 mg/dl), which did not differ from median arterial meter bias of -5 mg/dl (-9 to -1 mg/dl; P = 0.32). All of the capillary and arterial glucose meter values met acceptability criteria for subcutaneous insulin dosing, whereas only 89% (327 of 368) of capillary and 93% (344 of 368) arterial glucose meter values met accuracy criteria for intravenous insulin infusion. Time, patient position, and diabetes status were not associated with meter bias. CONCLUSIONS: Capillary and arterial blood glucose measured using the glucose meter are acceptable for intraoperative subcutaneous insulin dosing. Whole blood glucose on the meter did not meet accuracy guidelines established specifically for more intensive (e.g., intravenous insulin) glycemic control in the acute care environment.

LPLRFamide exerts short-term anorexigenic effects that coincide with magnocellular division of the hypothalamic paraventricular nucleus activation.

LPLRFamide is a member of the RFamide peptide family that elicits an anorexigenic effect when centrally injected in chicks although the mechanism mediating this response is poorly understood. Therefore, the purpose of this experiment was to elucidate the hypothalamic mechanism of short-term anorexia after central administration of LPLRFamide in chicks. In Experiment 1 chicks centrally injected with LPLRFamide decreased food intake at 15min but not 30min following administration compared to vehicle-injected chicks. For Experiment 2, c-Fos immunoreactivity was quantified in several appetite-associated hypothalamic nuclei and in LPLRF-injected chicks, compared to vehicle-injected chicks, there was an increase in the number of reactive cells in the magnocellular division of the paraventricular nucleus. Lastly in Experiment 3, real time-PCR was performed and hypothalamic proopiomelanocortin (POMC) mRNA abundance was increased in LPRLFamide-injected chicks compared to vehicle-injected chicks. Thus, following central injection of LPLRFamide there is activation of the paraventricular nucleus of the hypothalamus and increased expression of hypothalamic POMC mRNA in chicks.

Mange Caused by a Novel Micnemidocoptes Mite in a Golden Eagle ( Aquila chrysaetos ).

A second-year, female golden eagle ( Aquila chrysaetos ) was live trapped in northern California because of severe feather loss and crusting of the skin on the head and legs. On physical examination, the bird was lethargic, dehydrated, and thin, with severe feather loss and diffuse hyperemia and crusting on the head, ventral wings, ventrum, dorsum, and pelvic limbs. Mites morphologically similar to Micnemidocoptes derooi were identified with scanning electron microscopy. The eagle was treated with ivermectin (0.4 mg/kg) once weekly for 7 weeks, as well as pyrethrin, meloxicam, ceftiofur crystalline free acid, and voriconazole. Although the eagle's condition improved, and live mites or eggs were not evident on skin scrapings at the time of completion of ivermectin treatment, evidence of dead mites and mite feces were present after the last dose of ivermectin. Two additional doses of ivermectin and 2 doses of topical selamectin (23 mg/kg) were administered 2 and 4 weeks apart, respectively. No mite eggs, feces, or adults were evident after treatment was completed. A second golden eagle found in the same region was also affected with this mite but died soon after presentation. This is the first report, to our knowledge, of successful treatment, as well as treatment with selamectin, of mites consistent with Micnemidocoptes species in any raptorial species.

Knemidocoptic mange in wild golden eagles, California, USA.

During 2012-2013 in California, USA, 3 wild golden eagles were found with severe skin disease; 2 died. The cause was a rare mite, most closely related to Knemidocoptes derooi mites. Cautionary monitoring of eagle populations, habitats, and diseases is warranted.

Immunosurveillance associated with upper respiratory symptoms in elite swimmers: The 8-month period leading into Commonwealth Games.

OBJECTIVES: To monitor individual mucosal immunity and identify potential risk factors of upper respiratory symptoms in elite swimmers over a competitive season. DESIGN: Eight-month longitudinal study, observing mucosal immunity, Epstein-Barr virus status, training loads and illness symptoms of elite international swimmers, leading into the Commonwealth Games 2018. METHODS: Participants were fourteen elite swimmers (age ±â€¯standard deviation = 19.9 ±â€¯0.8 years, height = 178.9 ±â€¯6.3 cm, and mass = 75.0 ±â€¯7.7 kg). Self-reported upper respiratory symptoms, training load and saliva samples were collected weekly. Venous blood samples were taken at study commencement to determine Epstein-Barr virus status. RESULTS: Throughout the study, 70 episodes of upper respiratory symptoms were recorded resulting in 34 days of missed training. Incidence (p = 0.001), severity (p = 0.022), and duration of upper respiratory symptoms (p = 0.001) were significantly higher during high training loads, compared to low. Eight swimmers (61 %) had evidence of past infection with Epstein-Barr virus, but this had no relationship with incidence, severity, or duration of upper respiratory symptoms (p > 0.05). Relative individual salivary immunoglobulin A concentration was 12 % lower when upper respiratory symptoms were present but was not statistically significant (p = 0.101). CONCLUSIONS: This study highlights the importance of individual athlete monitoring, to identify swimmers at increased illness risk. Identification of possible risk factors for upper respiratory symptoms, such as increased training load, may allow for modifications in training or other illness preventative strategies for elite swimmers.

Utilization of Neoadjuvant Therapy for Localized Gastric Gastrointestinal Stromal Tumors and the Association with Survival.

BACKGROUND: For gastric GISTs, neoadjuvant imatinib is most often reserved for tumors near the gastroesophageal junction, multi-visceral involvement, or limited metastatic disease. Whether localized gastric GISTs benefit from neoadjuvant therapy (NAT) remains unknown. We sought to examine factors associated with NAT utilization for localized gastric GISTs and evaluate implications on survival. METHODS: The National Cancer Database identified patients with localized gastric GISTs treated with NAT (2010-2020), excluding tumors extending beyond the gastric wall, located in the cardia, or with metastatic disease. Multivariable logistic regression assessed characteristics of NAT use. After 1:1 propensity score matching, Kaplan-Meier methods and multivariable Cox regression assessed overall survival (OS). RESULTS: Of 7,203 patients, 762 (10.6%) received NAT followed by resection. On multivariable analysis, increasing tumor size was associated with NAT use (<2.0cm vs 2.0-5.0cm OR:2.03, 95%CI 1.19-3.47, p=0.010; vs >5cm OR:16.87, 95%CI 10.02-28.40, p<0.001). After propensity score matching, 1,506 patients remained. Median OS for NAT was 46.0 months vs 43.0 months for resection (p=0.059) which was independently predictive of improved survival (HR:0.89; 95%CI 0.80-0.99, p=0.041). Subgroup analysis by tumor size showed no survival differences for tumors <2.0cm or 2.0-5.0cm. Median OS was higher for tumors >5.0cm treated with NAT (NAT:45.4 months [IQR 29.5-65.9]. vs upfront resection:42.3 months [26.9-62.8]) and associated with improved survival on multivariable analysis (HR:0.88; 95%CI 0.78-0.99, p=0.040). CONCLUSION: Although patients who received NAT had improved survival, this was primarily due to tumors >5.0cm. Expanding NAT selection criteria to include localized gastric GISTs >5.0cm may improve outcomes and warrants investigation through clinical trials.