First Cohort Of Patients Research Articles

Tubeless ureteroenteric anastomosis in robot-assisted radical cystectomy with intracorporeal urinary diversion does not increase the risk of anastomotic stenosis or postoperative complications.

The objective is to demonstrate that omitting ureteral stent placement in robotic intracorporeal urinary diversion does not lead to increased risk of perioperative complications, namely ureteral strictures or anastomotic leaks. We retrospectively reviewed the records of 68 consecutive patients who underwent robotic radical cystectomy with ileal conduit creation or orthotopic neobladder by a single surgeon between January 2020 and September 2023. Chronologically, the first cohort of patients had ureteral stents placed to bridge the ureteroenteric anastomosis, and in the second cohort, stenting was omitted. Cohort 1 consisted of 28 patients with surgeries performed between January 2020 and April 2021, while cohort 2 had 40 patients who underwent surgery from April 2021 to September 2023. The cohorts were well matched with regard to patient age, gender, ASA score and rate of neoadjuvant chemotherapy. The choice of urinary diversion was left to surgeon and patient preference, and there was no significant difference in the proportion of ileal conduits versus orthotopic neobladders within each cohort. Estimated blood loss, total operative time, inpatient length of stay and pathologic T and N staging did not statistically differ between the cohorts. Overall, there was no difference in the rates of postoperative ileus, ureteral stricture, anastomotic leak, infectious complications, and 30-day readmission rates between the groups. Tubeless ureteroenteric anastomosis in patients undergoing robotic radical cystectomy with intracorporeal diversion does not appear to increase the risk of anastomotic strictures or postoperative complications. Further prospective evaluation is warranted.

Surgical management of skull base chordomas and chondrosarcomas: insights from a national cohort study

ObjectiveSkull base chordoma and chondrosarcoma are distinct sarcomas of the skull base but share significant therapeutic challenges due to their proximity to critical neurovascular structures, making surgical resection difficult. We...

First Report on Chronic Granulomatous Disease from Nepal and a Review of CYBC1 Deficiency.

Chronic granulomatous disease (CGD) primarily results from inherited defects in components of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex. These include gene defects in cytochrome B-245/558 subunit α/β and neutrophil cytosolic factors 1, 2, and 4. Recently, homozygous loss-of-function variants in cytochrome B-245 chaperone 1 gene (CYBC1) have been discovered to cause CGD (CYBC1-CGD). Data on variant-proven CGD from low-income countries, the most underprivileged regions of the world, remain sparse due to numerous constraints. Herein, we report the first cohort of patients with CGD from Nepal, a low-income country in the Himalayas' challenging terrain. Our report includes a description of a new case of CYBC1 deficiency who was first diagnosed with CGD at our center. Only a dozen cases of CYBC1-CGD have been described in the literature thus far which have been reviewed comprehensively herein. Most of these patients have had significant infections and autoimmune/inflammatory manifestations. Pulmonary and invasive/disseminated bacterial/fungal infections were the most common followed by skin and soft-tissue infections. Inflammatory bowel disease (IBD) was the most common inflammatory manifestation (median age at diagnosis: 9 years) followed by episodes of recurrent/prolonged fever. Other autoimmune/inflammatory manifestations reported in CYBC1-CGD include acute pancreatitis, hemophagocytic lymphohistiocytosis, systemic granulomatosis, interstitial lung disease, arthritis, autoimmune hemolytic anemia, uveitis, nephritis, and eczema. Our analysis shows that patients with CYBC1-CGD are at a significantly higher risk of IBD-like illness as compared to other forms of CGD which merits further confirmatory studies in the future.

Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial

BackgroundThe Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort.MethodsIn this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters.ResultsThis analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters.ConclusionsAlthough TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency.Trial registrationNCT00489697, registration number of the STIC-AVASTIN trial.

Robotic Heller's cardiomyotomy for achalasia: early outcomes for a high-volume UK centre.

Heller's cardiomyotomy (HCM) is the gold standard treatment for achalasia. Laparoscopic HCM has been shown to be effective with low rates of symptom recurrence, though oesophageal mucosal perforation rates remain high. The aim of this prospective case series is to assess the short-term complication rates and perioperative outcomes for the first cohort of patients undergoing robotic-assisted HCM for achalasia in a single high-volume UK centre. Data were collected from a prospective cohort of patients who underwent robotic HCM at a single high-volume UK centre. Outcomes were assessed using the Eckhard score, which was calculated after their routine postoperative clinic appointments. Thirteen patients underwent robotic HCM during the study period; this is the second largest reported case series in the European literature. There were no intraoperative oesophageal perforations. Six patients were discharged as day cases, six patients were discharged on the first postoperative day and one patient's hospital stay was two nights. There was a single perioperative complication of urinary retention. All patients reported improvement of symptoms following their operation, and all had a postoperative Eckhard score of less than 3, indicating their achalasia was in remission. This cohort has demonstrated that robotic HCM has an exceptional safety profile and results in high levels of symptom resolution, even early in the learning curve. The robotic approach may be superior to laparoscopy as it allows more precise identification and dissection of the oesophageal muscle fibres, which likely reduces the risk of inadvertent mucosal damage or incomplete myotomy.

Radiofrequency ablation for thyroid nodules in Ecuador: a cross-sectional study

ObjectivesTo describe the demographic characteristics and clinical outcomes following the first cohort of patients with Bening Thyroid Nodule (BTN) and (Papillary Thyroid Microcarcinoma) (PTMC) treated with Radiofrequency Ablation (RFA)in Ecuador.MethodsSingle-center, cross-sectional study. We included adults undergoing RFA for BTN and PTMC between July 2019 and May 2022. Descriptive statistics and the Wilcoxon signed-rank test were used to compare some pre- and post-intervention outcomes.ResultsWe included 44 patients with 36 BTNs and eight PTMCs. The median age was 45.80 years (IQR 16–79 years), and most patients had normal thyroid function (72.72%). The median follow-up time was 7.80 months (IQR1.0-34.0). Nodules were primarily solid (43.21%) or predominantly solid (56.81%). The pre-RFA median volume in the benign lesions group was 10.30 ml (IQR 1.86–18.97). After ablation, the 1-month, 3-month, 6-month, and 12-month median volumes were 6.90 (IQR 0.48–10.15; p < 0.01) mL, 5.72 (IQR 0.77–7.25; p = 0.045); 0.98 (IQR 0.25–3.64; p < 0.01), and 0.11 (IQR 0.07–11.26; p = 0.026), respectively. The volume rate reduction was 47.20%, 72.20%, 74.00%, and 96.20% at 1, 3, 6, and 12-month follow-ups, respectively. The pre-RFA median volume in the PTMC group was 0.25 ml (IQR 0.19–0.48). After ablation, the 1-month, 3-month, and 6-month mean volumes were 0.19 (range 0.12–0.31; p = 0.120) mL, 0.10 (IQR 0.05–0.15; p = 0.13), and 0.01 (IQR 0.005–0.04; p = 0.364), respectively.ConclusionsIn this first report from Ecuador, we found that RFA may be a feasible alternative for treating benign and malignant thyroid nodules in the short term. Long-term data are needed to evaluate oncologic outcomes in PTMC patients.

Placenta Accreta Spectrum Prophylactic Therapy for Hyperfibrinolysis with Tranexamic Acid.

To report on prophylactic therapy for hyperfibrinolysis with tranexamic acid (TXA) during expectant management (EM) in the placenta accreta spectrum (PAS). This is a monocentric retrospective study of women with PAS presenting at our hospital between 2005 and 2021. All data were retrospectively collected through the departmental database. 35 patients with PAS were included. EM was planned in 25 patients prior to delivery. Complete absorption of the retained placenta was seen in two patients (8%). Curettage was performed in 14 patients (56%). A hysterectomy (HE) was needed in seven (28%) patients; 18 patients (72%) underwent uterus-preserving treatment without severe complications. The mean duration of EM was 107 days. The mean day of onset of hyperfibrinolysis and beginning of TXA treatment was day 45. The mean nadir of fibrinogen level before TXA was 242.4 mg/dL, with a mean drop of 29.7% in fibrinogen level. Our data support EM as a safe treatment option in PAS. Hyperfibrinolysis can be a cause of hemorrhage during EM and can be treated with TXA. To our knowledge, this is the first cohort of patients with EM of PAS in whom coagulation monitoring and use of TXA have been shown to successfully treat hyperfibrinolysis.

Audit of lung SABR treatment concordance with national guidelines, in the first cohort of patients at Portsmouth University Hospital

Audit of lung SABR treatment concordance with national guidelines, in the first cohort of patients at Portsmouth University Hospital

AI Deployment on GBM Diagnosis: A Novel Approach to Analyze Histopathological Images Using Image Feature-Based Analysis.

Glioblastoma (GBM) is one of the most common malignant primary brain tumors, which accounts for 60-70% of all gliomas. Conventional diagnosis and the decision of post-operation treatment plan for glioblastoma is mainly based on the feature-based qualitative analysis of hematoxylin and eosin-stained (H&E) histopathological slides by both an experienced medical technologist and a pathologist. The recent development of digital whole slide scanners makes AI-based histopathological image analysis feasible and helps to diagnose cancer by accurately counting cell types and/or quantitative analysis. However, the technology available for digital slide image analysis is still very limited. This study aimed to build an image feature-based computer model using histopathology whole slide images to differentiate patients with glioblastoma (GBM) from healthy control (HC). Two independent cohorts of patients were used. The first cohort was composed of 262 GBM patients of the Cancer Genome Atlas Glioblastoma Multiform Collection (TCGA-GBM) dataset from the cancer imaging archive (TCIA) database. The second cohort was composed of 60 GBM patients collected from a local hospital. Also, a group of 60 participants with no known brain disease were collected. All the H&E slides were collected. Thirty-three image features (22 GLCM and 11 GLRLM) were retrieved from the tumor volume delineated by medical technologist on H&E slides. Five machine-learning algorithms including decision-tree (DT), extreme-boost (EB), support vector machine (SVM), random forest (RF), and linear model (LM) were used to build five models using the image features extracted from the first cohort of patients. Models built were deployed using the selected key image features for GBM diagnosis from the second cohort (local patients) as model testing, to identify and verify key image features for GBM diagnosis. All five machine learning algorithms demonstrated excellent performance in GBM diagnosis and achieved an overall accuracy of 100% in the training and validation stage. A total of 12 GLCM and 3 GLRLM image features were identified and they showed a significant difference between the normal and the GBM image. However, only the SVM model maintained its excellent performance in the deployment of the models using the independent local cohort, with an accuracy of 93.5%, sensitivity of 86.95%, and specificity of 99.73%. In this study, we have identified 12 GLCM and 3 GLRLM image features which can aid the GBM diagnosis. Among the five models built, the SVM model proposed in this study demonstrated excellent accuracy with very good sensitivity and specificity. It could potentially be used for GBM diagnosis and future clinical application.

Patient-Adaptive Automated Segmentation in Daily kVCT Images for Radiotherapy of Head and Neck and Prostate Cancer

The purpose of this study was to examine the use of transfer learning in deep learning-based auto-segmentation of daily kilovoltage computed tomography (kVCT) images for patient-specific adaptive radiotherapy. Using data from the first cohort of patients treated with the innovative BgRT system, the objective of this study was to evaluate the potential benefits of this approach in facilitating efficient and effective adaptive radiotherapy. For the head and neck (HaN) site and pelvic site, we first trained a deep convolutional segmentation network using a population dataset, consisting of 67 and 56 patient cases, respectively. This population network was then fine-tuned for a specific patient using a transfer learning approach, adapting the network weights. The auto-segmentation network utilized in this study was a 23-layer U-Net with batch normalization, a dropout rate of 0.5, and four skip connections between the encoder and decoder at different levels. We used initial planning CT and 5-26 sets of daily kVCT scans with a total of 8,039 images for patient-specific learning in the 6 HaN cases and 4 pelvic cases, particularly analyzing the relationship between the number of sequential patient-specific training data and the performance of the auto-segmentation. We compared the performance of the patient-specific network with the population network and the clinical rigid registration method, using the Dice similarity coefficient (DSC) as the evaluation metric. Additionally, we investigated the corresponding dosimetric impacts of the different auto-segmentation and registration methods. The patient-specific network showed improved mean DSC scores of 0.88 and 0.90 for three HaN organs at risk (OARs) and eight pelvic targets and OARs, respectively, compared to the population network (0.70 and 0.63) and the registration method (0.72 and 0.72). The DSC of the patient-specific network steadily improved as the number of longitudinal training cases increased, reaching near saturation after 6 training cases. The use of the patient-specific auto-segmentation resulted in a reduction of the mean discrepancy in target and OAR doses between delivery and planning from 5.5% with the clinical rigid registration to 1.1%. The use of patient-specific transfer learning in auto-segmenting kVCT images showed higher accuracy compared to a conventional population network and clinical registration-based method. This approach holds promise for enhancing dose evaluation accuracy in adaptive radiotherapy.

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

BackgroundAlthough bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features.ResultsOf the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis.ConclusionsThe data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy.

Omnipolar versus bipolar mapping to guide ventricular tachycardia ablation

Omnipolar technology (OT) was recently proposed to generate electroanatomical voltage maps with orientation-independent electrograms. We describe the first cohort of patients undergoing ventricular tachycardia (VT) ablation guided by OT. The purpose of this study was to compare omnipolar and bipolar high-density maps regarding voltage amplitude, late potentials (LP) annotation, and isochronal late activation maps (ILAM) distribution. A total of 24 patients (16 ischemic cardiomyopathy, 12 redo cases) underwent VT ablation under OT guidance. Twenty-seven sinus rhythm substrate maps and 10 VT activation maps were analyzed. Omnipolar and bipolar (HD Wave solution) voltages were compared. Areas of late potentials were correlated to the VT isthmuses areas and late electrograms misannotation was evaluated. Deceleration zones based on ILAM were analysed by 2 blinded operators and compared to the VT isthmuses. Omnipolar maps had higher points density (13.8 vs 8.0 points/cm2). Omnipolar points had 7.1% higher voltages than bipolar points within areas of dense scar and border zone. The number of misannotated points was significantly lower in omnipolar maps (6.8% vs 21.9%, p=0.01), showing comparable sensitivity (53% vs 59%) but higher specificity (79% vs 63%). The sensitivity and specificity of deceleration zones detection of the VT critical isthmus were respectively 75% and 65% for OT, and 35% and 55% for bipolar. At 8.4 months, 71% freedom from VT recurrence was achieved. OT is a valuable tool for guiding VT ablation, providing more accurate identification of late potentials and isochronal crowding due to slightly higher voltages.

P-105 COLSTAR study: Safety data on the first cohort of patients from the safety lead-in part of the study

P-105 COLSTAR study: Safety data on the first cohort of patients from the safety lead-in part of the study

Omnipolar mapping in ventricular tachycardia: will it be a game changer?

Abstract Funding Acknowledgements Type of funding sources: None. Background Ventricular tachycardias(VT) are life-theatening cardiac arrhythmias. Catheter ablation, the standard approach to VT is relying heavily on maps depicting intracardiac signals. The current mapping approach was based on bipolar electrograms, which are massively influenced by the direction of the underlying tissue activation. The omnipolar (OT) electrogram method was recently proposed to generate orientation-independent electrograms and has shown improved results in recent publications (1-2). We describe the first cohort of patients ablated for VT with the help of an OT-enabled catheter. Purpose To evaluate acute and mid-term follow-up of patients ablated for VT using an OT enabled mapping system. Methods Eighteen patients (age 65 ± 19; 2 females, 32% nonischemic, median ejection fraction 40), underwent catheter ablation for scar-related VT. 50% (9) n patients had previous ablation, 4 of which underwent epicardial access. High-density omnipolar maps were obtained with an HD-grid catheter after which ablation was performed with an irrigated-tip catheter. In all patients the ablation was primarily substrate-based with the support of CT scan scar visualization. In 18 patients local abnormal ventricular activities (LAVA) ablation was performed (3), while one patient showed no LAVA. In 7 patients VT mapping was possible due to stable blood pressure during the tachycardia. The median radiofrequency application duration was 36 min. While all patients except one were inducible at the beginning of the procedure, only 3 patients were inducible at the end with a protocol using up to 3 extrastimuli. Follow-up was available in 13 patients (7.1 ± 2.5 months) with 66% freedom from VT recurrence (60% in redo cases and 71% in first procedures). Conclusion OT is a reliable method to visualize signals and perform a substrate-based ablation in with good acute and mid-term outcomes. Future studies will evaluate the impact on long term outcomes.

High liver fibrosis scores in MAFLD patients are associated with adverse atrial remodeling and related clinical outcomes

Atrial fibrillation (AF) is the most common arrhythmia in the world, linked to a remodeled left atrium. A number of epidemiological studies have suggested an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and the incidence of AF. However, the pathogenesis leading to AF in the context of MAFLD remains unclear. We aimed at assessing the impact of MAFLD and liver fibrosis status on left atrium (LA) structure and function. Using two distinct cohorts, the patient's liver status is determined using validated blood biomarkers and clinical-biological scores (FLI, NFS). In the first cohort of patients undergoing AF ablation, the LA structural and functional impact of MAFLD was assessed by LA strain analysis and endocardial voltage mapping. Histopathological assessment of atrial fibrosis was performed in the second cohort of patients undergoing cardiac surgery. Finally, the impact of MAFLD on AF recurrence following catheter ablation was assessed. In the AF ablation cohort (n = 245), MAFLD patients with high risk of F3–F4 liver fibrosis presented more LA low-voltage areas compared to patients without MAFLD, impaired LA reservoir function assessed by peak left atrial longitudinal strain, and increased LA volume. Accordingly, among the MAFLD patients, those with a high risk of F3–F4 liver fibrosis presented a higher rate of AF recurrence during follow-up. These patients had permanent recurrent AF, therefore difficult to treat. In the cardiac surgery cohort (n = 20), an increase in histopathological atrial fibrosis was observed in MAFLD patients with a high risk of F3–F4 liver fibrosis. We found that liver fibrosis scoring in MAFLD patients is associated with adverse atrial remodeling and AF recurrences following catheter ablation. The impact of the management of MAFLD on LA remodeling and AF ablation outcomes should be assessed in dedicated studies. This work has been published in Frontier In Endocrinology in August 2022 (doi: 10.3389/fendo.2022.957245).

Abstract P4-03-43: Disease characteristics and outcomes of people with metastatic breast cancer in a single center cohort study: The Dallas Metastatic Breast Cancer Study

Abstract Background: Breast cancer is the most common cancer in women, and metastatic disease accounts for most breast cancer related deaths. Identifying risk factors for the onset and progression of metastatic breast cancer (MBC) can help us understand how to address and improve morbidity and mortality due to MBC. Large national databases, such the Surveillance, Epidemiology, and End Results (SEER) Program are limited in their ability to capture granular details from patients’ cancer histories. The Dallas Metastatic Breast Cancer Study (DMBCS) is a clinical database established at a single academic medical system to track patient demographics, associated pathology, treatments, and other variables to improve outcomes for patients with MBC. Methods: The DMBCS database was generated from a registry of breast cancer patients submitted to the National Cancer Institute from 2010 to 2021. Patients were initially excluded if they were identified as non-metastatic from this list. Chart review was then done to identify MBC patients from this subsequent group. Demographics, clinical history, pathologic features, lines of treatment, and subsequent recurrences were collected for all patients. Clinical data was stored in REDCap, a secure data collection platform for entering and managing data. Results: 230 cases were included in this preliminary data set. Of the 230 cases, 185 cases were metastatic at time of diagnosis while 45 cases were metastatic recurrences of breast cancer. At diagnosis, 14.8% were less than 40 years of age, 17.3% were 40-49, 35.7% were 50-59, 18.7% were 60-69, and 13.5% were greater than 70 years of age. In terms of ethnicity, 63.5% were White, 27.4% were Black, and 21.7% identified as Hispanic. At time of diagnosis, 30.9% of patients had a BMI classified as overweight and 40.4% were considered obese. Medical comorbidities included hypertension in 43% of cases, diabetes (18.3%), hyperlipidemia (27.4%), and autoimmune disease (13.0%). Clinical subtype analysis revealed 57.8% of patients were hormone receptor positive, 24.8% HER2 positive, and 17.4% triple negative, at diagnosis. 14.8% of cases were diagnosed as inflammatory breast cancer. The most common site of metastasis at presentation was bone with 69.1% of cases, followed by lung (33.9%), liver (30.0%), and brain (15.2%). Over 90% of patients were treated with at least one antineoplastic regimen and 39.6% underwent at least 4 therapies. Calculated 1-year survival after diagnosis was 85.7%. Conclusions: The introduction of the DMBCS will allow continued investigation into clinical drivers of MBC. In this first cohort of patients, we characterized key, yet often underreported, variables and outcomes. Potential applications of this database include investigating the association between obesity and overall survival in patients with MBC, understanding how socioeconomic disparities affects outcomes of patients with MBC, and exploring correlations between autoimmune disease and the progression of MBC. Citation Format: Meng Cao, Mir Lim, Anna Moscowitz, Jonathan Ladner, Christine Hodgdon, Julia Maues, Sangeetha Reddy, Isaac Chan. Disease characteristics and outcomes of people with metastatic breast cancer in a single center cohort study: The Dallas Metastatic Breast Cancer Study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-43.

Molecular Aberrations in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome with Excess Blast II (MDS-EB II) in Kuwait

Introduction: AML is a heterogeneous disease. Different mutational profiles have been described and correlate with variable outcomes. Genetic abnormalities are not well-described in our region. Our aim is to describe the molecular aberrations observed in the first cohort of patients. We recently introduced DNA based Oncomine Myeloid Gene Panel testing 55 genes. Method: we collected clinical, cytogenetic and molecular data prospectively since we introduced the test in late 2020. We also reviewed medical charts to collect baseline clinical data. We included patients aged 16 yrs and above with AML or MDS-EB II treated at Kuwait Cancer Center. Results: fifty-seven patients were included in the study with median age of 51 yrs. Almost one third of the patients were Kuwaitis (36%). Baseline demographic described in (table 1). We have 53 patients with AML (92%), 3 patients with MDS-EB II (5%) and 1 pt with chronic myeloid leukemia in myeloid blast crisis (CML-MBC). Most of the patients had at least one mutation (91%) detected by the panel. The most common mutations (figure1) were FLT3 (ITD & D835) detected 26.3%, followed by NPM-1 detected in 21%. We have noticed an increased PTPN11 mutation, detected in 17.5% of the cases. Conclusion: This is an important study showing extensive molecular abnormalities in AML patients in the region. This will facilitate more understanding of the disease biology and potentially guide therapeutic options

Relapse Prophylaxis Post-Haploidentical Bone Marrow Transplantation and Cyclophosphamide (Haplo/Cy) By Infusion of Donor-Derived Expanded/Activated Gd T Cells: A Phase I Trial

Background: Effector γδ T cells immediately recognize and kill malignant cells in a broad-based non-MHC restricted manner. Increases in circulating donor-derived γδ T cells during post-bone marrow transplant (BMT) recovery have been significantly associated with improved disease-free survival (DFS). Relapse post Haplo/Cy BMT occurs in approximately 45% of patients. We sought to mitigate relapse in this context by expanding, activating, and infusing donor-derived haploidentical γδ T cells. We now report preliminary clinical and biologic correlative findings from the first cohort of patients who have been treated with ex vivo expanded and activated donor γδ T cells (EAGD). This single-center Phase I clinical trial represents the first systemic infusion of allogeneic EAGD cells in the post-BMT setting Methods: Standard of care reduced-intensity flu/cy/TBI conditioning was followed by an unmanipulated bone marrow graft and 50mg/m2 Cy on days +3 and +4 post-transplant. EAGD were manufactured using the Miltenyi Prodigy bioreactor and cryopreserved. The product was infused intravenously within 5 days of neutrophil engraftment (ANC >500/µL X 3d). Peripheral blood was collected at EAGD infusion and monthly thereafter through day +90, with additional collections every 6 months through 1 year. Biologic parameters included multiparameter flow cytometric immunophenotyping and single cell cytokine analysis of the EAGD graft. Peripheral blood analysis includes leukocyte count and differential, immunophenotyping, and serum Th1/Th2/Th17 cytokine analysis. Primary endpoints include dose-limiting toxicities (DLT) and grade 3-4 adverse events while secondary endpoints include incidence of acute and chronic GvHD, relapse, and overall survival. Results: Three patients have received the first dose level of 1 x 106 EAGD/kg. All three patients remain in morphologic complete remission at 26.5, 24.2, and 12.5 months post-BMT. One patient is receiving ongoing hypomethylating therapy for the occurrence of recipient chimerism. Grade 1-2 toxicities include constipation, CMV reactivation, emesis, fatigue, and hypomagnesaemia. Steroid-responsive cutaneous acute Grade I-II GVHD has been observed in all patients with one patient experiencing Grade II intestinal GvHD. No chronic GVHD, DLTs, treatment-related ≥ grade 3 adverse events, or cytokine release syndrome has occurred. EAGD grafts contained 88.7% - 99.2% Vγ9Vδ2+ γδ T cells with small populations of NK cells and <1.0 x 10 αβ T cells/kg. EAGD principally expressed Granzyme B, MIP1α, MIP1β, and IL-2. Significant peripheral lymphodepletion persisted through the first 100 days post-BMT followed by slow recovery of CD4+, CD8+, γδ T and B cells. NK cells remained within the low normal range throughout. T cells transitioned from a CD45+CD27- effector phenotype to CD45RA CD27 central to effector memory phenotype as recovery progressed. CD3 CD4 CD25 FoxP3 Treg cells remained <3% of circulating T cells. Preliminary serum cytokine and chemokine analysis revealed predominant expression of IFNγ, IL-12p70, IP-10, RANTES and TNFα. Conclusions: Early indications suggest that EAGD transfusion with the initial dose level of 1 x 106 EAGD/kg has manageable toxicity and an appropriate immune recovery profile with 3 of 3 patients alive and progression-free. Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03533816

Clinical Outcomes after MRI Guided Stereotactic Body Radiotherapy for (Peri-) Pancreatic Tumors

<h3>Purpose/Objective(s)</h3> Radiotherapy treatment of pancreatic cancer can be challenging due to close relationship between the tumor and radiosensitive intestines and poor visibility of the upper abdomen with conventional treatment methods. In recent years, with the introduction of MR-guided radiotherapy (MRgRT) it became possible to deliver ablative doses to (peri-)pancreatic tumors. In this multicenter cohort study, we report clinical outcomes from our first cohort of patients with (peri-)pancreatic tumors with MR-guided stereotactic radiotherapy on a 1.5 T MR-Linac. <h3>Materials/Methods</h3> All patients with (peri-)pancreatic tumors treated on the 1.5 T Unity MR-Linac between April 2019 and January 2022 at two institutes. Symptoms were reported using clinician-reported outcome measurements defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Quality of life (QoL) was assessed with the EORTC QLQ-C30 questionnaire and evaluated with the Global Health status. Symptoms and QoL were assessed at baseline, and at three, six and twelve months after treatment. The Kaplan-Meier analysis was performed for the 6 months-, and 1-year survival. <h3>Results</h3> The baseline characteristics of 79 patients are summarized in Table 1. The most frequently delivered SBRT scheme was 40 Gy in 5 fractions of 8 Gy. Most frequently reported grade 3 symptoms at baseline, three months follow-up, six months, and twelve months were abdominal pain (0%, 13%, 3%, and 5%); anorexia (0%, 9%, 0%, and 0%); fatigue (0%, 5%, 6%, and 5%); nausea (0%, 5%, 0%, and 5%), and diarrhea (0%, 5%, 6%, and 5%). Other grade 3 toxicity at three months follow up occurred in 5% for malabsorption; 2% of patients for vomiting; 2% for gastroparesis; 2% for weight loss; 2% for portal hypertension and 2% for gallbladder obstruction. No treatment-related toxicities higher than grade 3 were observed in our cohort. The EORTC Global Health status was 71 at baseline (n=37), 70 after three months follow up (n=20), 65 after six months (n=12), and 67 after twelve months (n=6). From the treatment start with MRgRT, the cumulative 6 months- and 1-year survival was 88%, and 74%, respectively. <h3>Conclusion</h3> In this international prospective cohort of patients with (peri-)pancreatic tumors, we observed a low incidence of major treatment-related toxicity and a stable Global Health status at three months post MRgRT on a 1.5T MR-Linac.

AML-419 Molecular Aberrations in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome With Excess Blast II (MDS-EB II) in Kuwait

AML is a heterogeneous disease. Different mutational profiles have been described and correlate with variable outcomes. Genetic abnormalities are not well-described in our region. Our aim is to describe the molecular aberrations observed in the first cohort of patients. We recently introduced DNA based Oncomine Myeloid Gene Panel, testing 55 genes. We collected clinical, cytogenetic and molecular data prospectively since we introduced the test in late 2020. We also reviewed medical charts to collect baseline clinical data. We included patients aged 16 yrs and above with AML or MDS-EB II treated at Kuwait Cancer Center. Fifty-seven patients were included in the study with median age of 51 yrs. Almost one third of the patients were Kuwaitis (36%). We have 53 patients with AML (92%), 3 patients with MDS-EB II (5%), and 1 patient with chronic myeloid leukemia in myeloid blast crisis (CML-MBC). Most of the patients had at least one mutation (91%) detected by the panel. The most common mutations were FLT3 (ITD & D835), detected 26.3%, followed by NPM-1, detected in 21%. We have noticed an increased PTPN11 mutation, detected in 17.5% of the cases. This is an important study showing extensive molecular abnormalities in AML patients in the region. This will facilitate more understanding of the disease biology.