Surgical Resection Of Tumor Research Articles

Outcomes of Trigeminal Ganglion Sparing Surgical Resection of Nonacoustic Cerebellopontine Angle Tumors Causing Trigeminal Neuralgia

ObjectiveTumors may be responsible for up to 5% of trigeminal neuralgia (TN) cases. Predictors of long-term pain relief after surgical resection of various cerebellopontine angle (CPA) tumor types are not well understood. Previous studies found that size and extent of resection predict long-term pain status, although resection of tumor involving the trigeminal ganglion (TG) may be associated with high morbidity. This study evaluated predictors of TN pain freedom after resection of a non-acoustic CPA tumor, with avoidance of any portion involving the TG. MethodsIn a retrospective cohort study, we evaluated clinical outcomes and complications after surgical resection of non-acoustic CPA tumors with purposeful avoidance of the TG causing trigeminal neuralgia. The primary outcome was pain-freedom. We performed logistic regression analyses to examine the relationship between pain-freedom at last follow-up and age, side of symptoms, pre-operative symptom duration, tumor diameter, tumor type, and concurrent neurovascular compression (NVC). ResultsOf 18 patients with non-acoustic CPA tumors causing TN treated with surgical resection, 83.3% were pain-free at last follow-up (mean 44.6 months). Age(p=0.12), side (p=0.41), pre-operative symptom duration(p=0.85), tumor diameter(p=0.29), tumor type(p=0.37), and NVC presence (p=0.075) were not associated with long-term pain freedom. ConclusionsThis study provides additional evidence that various tumor types causing trigeminal neuralgia may safely undergo surgical resection and decompression of the trigeminal nerve to treat TN. This study presents a cohort of patients that underwent resection of a non-acoustic CPA tumor, with purposeful avoidance of the TG to minimize complications, demonstrating high rates of long-term pain freedom.

The association of the neutrophil-tolymphocyte ratio and postoperative complications in colorectal cancer surgery: A scoping review

Background: Surgical resection of tumours is usually performed in patients with colorectal carcinoma regardless of the disease’s stage. Nonetheless, before undergoing surgery, it is important to be aware that various postoperative complications may arise. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker related to complications following surgical operations. Hence, the present review study was undertaken to assess the association of the NLR and postoperative complications in resections of colorectal tumours. Methods: Major electronic databases were searched to find all available existing literature. Data was extracted and processed from the eligible studies and presented in the present review. Results: Overall, a total of 32 observational and case-control studies consisting of 9095 colorectal cancer patients were included in the review. In 27/32 of the studies, a statistically significant positive association was found between the NLR and post-operative complications. Preoperative NLR was assessed in 25/32 of the studies and postoperative NLR was assessed in 8/32 of the studies including studies in which NLR was assessed in both moments. Conclusions: High preoperative and postoperative values of the NLR increase the risk of developing postsurgical complications. However, it is important to conduct further prospective cohort studies to verify the results and deepen knowledge in this area.

Incidence of avascular necrosis of native femur following hip transposition surgery for periacetabular malignancies: a single-centre experience.

Hip transposition surgery after surgical resection of large pelvic tumours is a well-established alternate to endoprosthetic reconstruction. The major goals of surgery are to ensure adequate resection margins with limb salvation, albeit with acceptable levels of morbidity. While surveillance is aimed at diagnosing local recurrence or distant metastasis primarily, other complications may occasionally be seen.The aim of this study was to assess incidence of avascular necrosis (AVN) in the preserved native femoral heads after hip transposition surgery for periacetabular malignancies, also known as hanging hip surgery. Patient records and follow-up imaging of 22 patients who had undergone hanging hip surgery from 1999 to 2020 were retrospectively analysed to assess for any probable causes of AVN. Of the 22 patients, 5 (22.7%) had developed AVN on follow-up with a mean time of onset of about 10.5 months from surgery (5 months-2 years). A review of the patient demographics, surgical notes, preoperative management did not offer any clues as to the cause of AVN in these patients. Osteopenia was the most common radiological finding (59%) in most patients, but this also did not herald AVN onset. The theory that loss of major vascular supply to the femoral head from capsular disruption during hip transposition surgery would lead to AVN in most patients did not hold true as AVN occurred in a small number of patients.

200 DWI and ADC Changes in Patients With Glioblastoma IDH-Wild Type Following Surgical Tumor Resection

INTRODUCTION: Current standard of care for glioblastoma (GBM) entails maximal tumor resection to achieve better outcomes while preserving neurological function. Early postoperative DWI has elucidated that peritumoral ischemia is common following glioma resection, but radiographic characteristics, risk factors, and outcomes have not been well described. METHODS: This retrospective cohort included 324 patients (18-86 years) who underwent surgical resection for glioblastoma IDH-wildtype between 2005 and 2022. All patients had structural MRI and DWI acquired preoperatively and within 72 hrs after resection. Areas of restricted diffusion on postoperative DWI were classified as rim, sector, mixed, or remote. RESULTS: Areas of restricted diffusion on postoperative DWI were found in 173 (53%) patients. 55 (32%) were rim-shaped, 103 (59%) sector-shaped, 10 (6%) mixed, and 5 (3%) remote. Preoperative tumor volume was positively correlated with areas of ischemia (p = 0.048), but peritumoral DWI was not correlated with decreased overall survival (OS) or Karnofsky Performance Score (KPS). In the full cohort analysis, gross total resection (GTR) correlated with improved OS compared to subtotal total resection (STR) (p = 0.016); however, subgroup analysis revealed that this survival benefit was exclusively found in patients without peritumoral infarction on DWI (21 months vs. 13 months, p = 0.043). CONCLUSIONS: Larger tumor volume was a risk factor for larger peritumoral infarction. The survival benefit of GTR was only seen in patients who did not experience postoperative peritumoral infarction, underscoring the importance of maximal safe tumor resection. Future study on specific causes of postoperative peritumoral infarctions may improve surgical management and outcomes in glioblastoma patients.

Video-fluorescence navigation by PpIX and tissue saturation measurement during surgical resection of gastric malignant tumor

SignificanceThe quality of the anastomosis is an important factor influencing the outcome of the surgical operation. Since it provides a reliable connection of sutured biological tissues, it is necessary to control the consistency of the anastomosis in order to prevent complications after the operation. Fluorescence diagnostics makes it possible to determine the localization of the tumor and residual pathological tumor tissues after resection by the intensity of the photosensitizer fluorescence accumulated in tissue, which can be missed during visual examination. ApproachFluorescence diagnostics was performed using a diode laser with a wavelength of 635 nm, which is at the absorption peak of the photosensitizer protoporphyrin 9 (PpIX). The assessment of the StO2 level was carried out spectroscopically using white broadband radiation. ResultsThe tissue blood supply was assessed. Patients with stomach resection underwent fluorescent diagnostics using PpIX. The localization of the tumor and pathological tumor sites after partial resection of the stomach was determined. The change in the level of StO2 at each stage of the operation was determined. ConclusionsFluorescent diagnostics using PpIX and joint determination of StO2 by diffuse scattering spectroscopy improved the quality of tumor resection and assessed the state of gastric tissue blood supply in real time.

Scoliosis After Resection of Primary Pediatric Chest Wall Tumors

BackgroundScoliosis is one of the long-term consequences of surgical resection of pediatric chest wall tumors. This study aimed to identify the risk factors associated with scoliosis development following the resection of chest wall tumors. MethodsRetrospective cohort study of 64 children who underwent resection of malignant chest wall tumors from 2009 to 2022. Univariate and multivariate analyses were used to investigate factors associated with scoliosis development. ResultsThe median age at the time of surgery was 7 years (range, 3–21), with 33 (51.6%) patients undergoing surgery before the age of 10 years. The most common histology was Ewing sarcoma (n = 57). A median of 3 (range, 1–5) contiguous ribs were resected. A total of 34 (53.1%) patients had anterior CWTs and 30 (46.9%) had posterior CWTs. Concomitant partial lung and diaphragmatic resection were performed in 12 patients (lung, n = 7; diaphragm, n = 5). Scoliosis convex towards the resection side developed in 21 (32.8%). The primary risk factors for scoliosis were resecting 3 or more ribs (OR 6.44) and resection of the posterior rib segment (OR 5.49). Patients with a tumor resection below 10 years old were not associated with a higher risk of scoliosis. ConclusionsScoliosis following resection of a primary malignant pediatric chest wall tumor is associated with resection involving three or more ribs and resection of the posterior rib sector. Type of StudyRetrospective observational. Level of EvidenceIV.

Reactive Oxygen Species Explicit dosimetry for Pleural PDT

SignificancePreclinical studies show improved prediction of treatment outcome using [ROS]rx than light fluence rate or PDT dose. We demonstrate ROSED in a clinical setting. ApproachExplicit dosimetry of light fluence, photosensitizer concentration, and oxygen concentration is used to quantify the reactive oxygen species explicit dosimetry (ROSED) during Photofrin-mediated pleural PDT. Light fluence and photosensitizer concentration were measured by a customized multi-channel PDT dose dosimeter system. Diffuse correlation spectroscopy (DCS) contact probes were sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (BFI) during intraoperative PDT treatment. Tissue oxygen concentration can be determined by utilizing tumor blood flow measured by DCS. ResultsLarge inter- and intra-patient heterogeneities in [ROS]rx were observed although an identical light dose of 60 J/cm2 was prescribed to all patients. ConclusionsThis study summarizes the current results of ROSED for a Phase II pleural PDT clinical trial.

The supraclavicular approach in the management of cervicothoracic-junction benign neurogenic tumors: A real-world analysis

ObjectivesThe study objectives were to evaluate the safety, feasibility, and risk of neurologic complications with the supraclavicular approach in the operative management of cervicothoracic-junction benign neurogenic tumors. MethodsBetween January 2012 and April 2023, 115 patients who underwent surgical resection for cervicothoracic-junction benign neurogenic tumors were retrospectively enrolled. Patients were divided into 3 groups based on the surgical approach: supraclavicular alone (Supraclav-Alone), n = 16; Transthoracic-Alone (video-assisted thoracoscopic surgery/Open), n = 87; and supraclavicular combined with transthoracic (Supraclav + video-assisted thoracoscopic surgery/open), n = 12. Clinicopathologic variables and postoperative morbidity including neurologic complications were summarized among the groups. Logistic regression analysis was performed to identify predictors for long-term (>6 months) brachial plexus injuries. ResultsThe cohort comprised 28 patients (24.3%) who underwent surgical resection using a supraclavicular approach. The Supraclav-Alone group portended the most cephalad location of tumor, the smallest pathologic tumor size, the shortest operative time, the least blood loss, and the least postoperative pain. The incidence of surgical complications, phrenic nerve neuropraxia, recurrent laryngeal nerve neuropraxia, or Horner’s syndrome was similar among the groups postoperatively. However, use of the supraclavicular-alone approach (adjusted odds ratio, 0.165; 95% CI, 0.017-0.775) was a predictor for long-term brachial plexus injury complications. Among patients who experienced brachial plexus injury complications, the proportion of patients achieving complete resolution was higher among those undergoing a supraclavicular approach group (Supraclav-Alone: 80.0% vs Supraclav + video-assisted thoracoscopic surgery/Open: 60.0% vs video-assisted thoracoscopic surgery/Open: 25.8%). ConclusionsThe supraclavicular approach may be a safe and feasible strategy in the management of cervicothoracic-junction benign neurogenic tumors that does not increase surgical complications and minimizes the severity of brachial plexus injury.

Using photodynamic approaches to improve the diagnostic accuracy of image guided surgery

SignificanceIncomplete surgical resection of tumors using white light and preoperative imaging causes tumor reoccurrence. Antibody-dye conjugate can target and accumulate into the tumor but has longer wait times for surgery following administration. This process can be expedited using PDP which not only increase the delivery but also improves the diagnostic accuracy in tumor detection. ApproachThe mice bearing FaDu head and neck tumors were administered with Cetuximab-IRDye800 (Cet-IRDye800) and treated with sub-therapeutic dose of PDT (photodynamic Priming; PDP). The accumulation and distribution of Cet-IRDye800 into the tumor were measured and analyzed. ResultsPDP improves and expedites the delivery of Cet-IRDye800 into the tumors significantly. It also improves diagnostic accuracy in tumor detection with respect to the vicinal salivary gland. ConclusionsThis study highlights, for the first time, that PDP enhances the rate and extend of delivery of the fluorescently labeled antibodies for the effective photodynamic image guided surgery.

POSTOPERATIVE RADIOTHERAPY IN SALIVARY DUCTCARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE

Salivary duct carcinoma(SDC) is a rare and aggressive tumor of the salivary glands that often occurs in men between the fifth and sixth decades of life. standard treatment is based on wide surgical resection of the primary tumor with lymph node dissection, followed by postoperative radiotherapy. The place of chemotherapy in the treatment of SDC remains unknown. In this publication, authors report a case of SDC of the left parotid gland. A 28-year-old male suffered from a painful neck mass associated with hearing loss that had been evolving for 6 months. The patient initially had a cervical CT scan and a parotid MRI, which showed a tumor of the left parotid gland. He initially had a total parotidectomy preserving the facial nerve with an ipsilateral neck dissection, as the intraoperative histological examination was in favor of malignancy. The final analysis of the surgical specimen concluded to a ductal carcinoma of the parotid with lymph node metastasis. Adjuvant radiation therapy has been indicated. The evolution was unfavorable due to the appearance of multisite metastases after one year.

Embolic Material Migration as the Predominant Contributing Factor to Prognostic Deterioration Following Combined Tumor Resection and Preoperative Embolization.

Introduction Preoperative embolization can potentially facilitate surgical resection of challenging tumors in the intracranial and facial regions; however, its clinical efficacy remains controversial, mainly due to potential morbidity risks. We explored negative factors of the combined treatment of preoperative embolization and tumor resection that affect neurological prognosis. Method This retrospective study used clinical data from 132 consecutive tumors that underwent combined treatment at multiple facilities between January 2016 and May 2021. Basic patient information, tumor characteristics, and treatment details were assessed to identify predictors of deterioration as measured using the modified Rankin scale (mRS) score at three months post-treatment. Results Among the 126 eligible combined treatments, a deterioration in the postoperative mRS score was observed in 19/126 (15.1%). Complications related to embolization and tumor resection occurred in 8/126 (6.3%) and 19/125 (15.2%) of procedures, respectively. Multivariate analyses indicated significant associations between migration of embolic material (adjusted odds ratio 13.80; 95% confidence interval 1.25-152.52; p=0.03), elevated intraoperative blood loss (p=0.04), and deterioration of postoperative mRS score. Embolic material migration was identified as the primary prognostic factor for the deterioration of score. An analysis of 192 procedures, excluding those that exclusively used coils, identified embolization targeting the accessory meningeal artery (p=0.046) and the third segment of the internal maxillary artery (p=0.03) as a risk factor for embolic material migration. Conclusions Embolic material migration is the predominant factor associated with declining neurological outcome that persists into the chronic phase after combined treatment. Given that preoperative embolization is a supplementary treatment option, a thorough understanding of vascular anatomy and striving safe procedure are critical.

Prognostic significance of systemic immune-inflammation index in patients with nonfunction pancreatic neuroendocrine tumor undergoing surgical resection.

The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune-inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow-up of 98 months. Univariate analysis showed that higher SII (p < 0.0001), tumor size >4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease-free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p < 0.0001) and G2/G3 grade (HR: 3.11; 95% CI: 1.42, 6.82; p = 0.005) remained significantly associated with tumor recurrence. Furthermore, 46 (12.6%) patients died during the follow-up. Higher SII (HR: 8.43; 95% CI: 3.19, 22.72; p < 0.0001) and G2/G3 grade (HR: 3.16; 95% CI: 1.01, 9.86; p = 0.048) were independent predictors of overall survival (OS) by multivariate analysis. In conclusion, our study revealed that a higher SII level was associated with tumor-related features (larger tumor size and advanced grade) and subsequent shorter DFS and OS in patients with nonfunctioning pNETs. These results indicated that the SII could serve as an efficient prognostic biomarker for nonfunctioning pNETs.

Surgical Resection of Primary Tumor for Bone Metastatic Breast Cancer Patients at Initial Presentation.

The purpose of this study was to investigate whether primary tumor resection in patients with bone metastatic breast cancer has an impact on survival using the Surveillance, Epidemiology, and End Results database, considering subtype classification. We included all female patients with bone metastatic breast cancer at initial presentation between 2010 and 2016 with known hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. Cases showing unknown cause of death or unknown HR/HER2 status were excluded. Survival analysis was performed using Cox proportional hazards modeling to calculate hazard ratios (HZR). Of the 13,450 patients included in this study, 2,073 patients were HR+/HER2+, 8,597 patients were HR+/HER2-, 797 patients were HR-/HER2+, and 1,182 patients were HR-/HER2- (triple-negative). Five-year overall survival (OS) rate was 34.5% in HR+/HER2+, 26.0% in HR+/HER2-, 29.2% in HR-/HER2+ and 8.0% in triple-negative. Triple-negative patients showed the worsen OS [HR+/HER2+: HZR=2.1, 95% confidence interval (CI)=1.9-2.3; HR+/HER2-: HZR= 2.4, 95%CI=2.2-2.6; HR-/HER2+: HZR=1.5, 95%CI=1.3-1.6]. After excluding patients who died within six months, primary tumor resection prolonged survival in each subtype classification except HR-/HER2+. Patients with triple-negative bone metastatic breast cancer showed unfavorable survival. Primary tumor resection prolonged survival in each subtype except for HR-/HER2+.

Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver.

Resection of hepatic metastasis from neuroendocrine tumors (NETs) improves quality of life and prolongs 5-year survival. Ablation can be utilized with surgery to achieve complete resection. Although several studies report long-term outcomes for patients undergoing ablation, none have explored perioperative effects of ablation in patients with metastatic NETs. To determine if intra-operative ablation during hepatectomy increases risk of adverse outcomes such as surgical site infections (SSIs), bleeding, and bile leak. A retrospective analysis of the hepatectomy National Surgical Quality Improvement Program database from 2015-2019 was performed to determine the odds of SSIs, bile leaks, or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone. Of the 966 patients included in the study, 298 (30.9%) underwent ablation during hepatectomy. There were 78 (11.7%) patients with SSIs in the hepatectomy alone group and 39 (13.1%) patients with a SSIs in the hepatectomy with ablation group. Bile leak occurred in 41 (6.2%) and 14 (4.8%) patients in the two groups, respectively; bleeding occurred in 117 (17.5%) and 33 (11.1%), respectively. After controlling for confounding variables, ablation did not increase risk of SSI (P = 0.63), bile leak (P = 0.34) or bleeding (P = 0.07) when compared to patients undergoing resection alone on multivariate analysis. Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection, bleeding, or bile leak. Surgeons should utilize this modality when appropriate to achieve optimal disease control and outcomes.

Infantile Myofibroma of the Frontal Bone: A Case Report

Background: Infantile myofibroma stands as the most prevalent fibrous neoplasm within the pediatric population, despite its rarity. The majority of these tumors manifest within the initial 2 years of life. Clinically, myofibroma lesions are classified into solitary and multicentric tumors. Methods: We present a case of infantile myofibroma located within the frontal bone of a 16-month-old infant. Initial evaluation of the swelling and its spread was conducted using CT and MRI scans. Subsequently, the diagnosis was confirmed through a core needle biopsy. Results: The tumor underwent surgical excision with 1 cm safety margin and immediate reconstruction with strips of calvaria bone graft. Histopathology of the specimen showed complete tumor clearance with actual margin of 7 mm. Conclusion: The surgical resection of cranial benign bone tumors should be meticulously planned with a multidisciplinary approach. Wherever possible, immediate reconstruction should be conducted to avoid the morbidity of a subsequent procedure.

Customised pre-operative cranioplasty to achieve maximal surgical resection of tumours with osseous involvement-a case series.

Surgical resection with bony margins would be the treatment of choice for tumours with osseous involvement such as meningiomas and metastasis. By developing and designing pre-operative customised 3D modelled implants, the patient can undergo resection of meningioma and repair of bone defect in the same operation. We present a generalisable method for designing pre-operative cranioplasty in patients to repair the bone defect after the resection of tumours. We included six patients who presented with a tumour that was associated with overlying bone involvement. They underwent placement of customised cranioplasty in the same setting. A customised implant using a pre-operative imaging was designed with a 2-cm margin to allow for any intra-operative requirements for extending the craniectomy. Six patients were evaluated in this case series. Four patients had meningiomas, 1 patient had metastatic breast cancer on final histology, and 1 patient was found to have an intra-osseous arteriovenous malformation. Craniectomy based on margins provided by a cutting guide was fashioned. After tumour removal and haemostasis, the cranioplasty was then placed. All patients recovered well post-operatively with satisfactory cosmetic results. No wound infection was reported in our series. Our series demonstrate the feasibility of utilising pre-designed cranioplasty for meningiomas and other tumours with osseous involvement. Following strict infection protocols, minimal intra-operative handling/modification of the implant, and close follow-up has resulted in good cosmetic outcomes with no implant-related infections.

Evaluation of the prognostic performance of different cutoff values of lymph node ratio staging system for stage III colorectal cancer.

This study attempted to compare the prognostic performance of lymph node ratio (LNR) staging system with different cutoff values relative to American Joint Committee on Cancer (AJCC) pN staging system in stage III colorectal cancer (CRC). Overall, 45,069 patients from the SEER dataset and 69 patients from the Second Affiliated Hospital of Nanjing Medical University (the External set) who underwent surgical resection of the primary tumor and were diagnosed with stage III CRC by postoperative pathology were included. Patients were divided into three subgroups based on the LNR cutoff used in previous studies, Kaplan-Meier curves were plotted, and log-rank test was used to compare the differences among groups in terms of cancer-specific survival (CSS). Cox regression model was applied for survival analysis. To evaluate the discriminatory power of different lymph node staging systems, Harrell's C statistic(C-index) and Akaike's Information Criterion (AIC) were applied. A set of optimal cutoff values (0.11; 0.36; 0.66) of LNR staging system with the most considerable discriminatory power to the prognosis in patients with stage III CRC (SEER set: C-index = 0.714; AIC = 58,942.46, External set: C-index = 0.809; AIC = 164.36) were obtained, and both were superior to the AJCC pN staging system (SEER set: C-index = 0.708; AIC = 59,071.20, External set: C-index = 0.788; AIC = 167.06). For evaluating the prognostic efficacy of patients with stage III colorectal cancer, the cutoff value (0.11; 0.36; 0.66) of LNR staging system had the best discrimination and prognostic ability, which was superior to LNR staging system under other cutoff values and AJCC pN staging system.

Abstract 6313: Enhancing CAR T cell-based immunotherapy outcomes in PDAC: Evaluating iC9.B7-H3 CAR T cells in adjuvant, neoadjuvant, and monotherapy settings

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive and lethal cancers worldwide. Despite negative margin resections and subsequent systemic therapy, PDAC often recurs. Additionally, most patients present with locally advanced and unresectable tumors at the time of diagnosis. Cancer-associated fibroblasts (CAFs) contribute to the highly desmoplastic tumor microenvironment (TME) and form a biophysical barrier, limiting immune cell infiltration. Moreover, CAF-secreted factors suppress the anti-tumor activity of T cells and shift cancer cells toward invasive proliferative and mesenchymal phenotypes. Therefore, targeting CAFs can enhance T-cell infiltration and improve the efficacy of T-cell based immunotherapeutic strategies. B7-H3 is an immune checkpoint molecule highly expressed on PDAC cells and CAFs. In this study, we investigate the use of Chimeric Antigen Receptor (CAR) T cells targeting B7-H3 to eliminate metastatic PDAC in a preclinical mouse model in three different settings: I. Adjuvant II. Neoadjuvant III. CAR T cell monotherapy. Our CART-B7-H3 construct includes an inducible caspase 9 (iC9) suicide gene, which allows for the controlled elimination of the CAR T cells in the event of overwhelming cytokine release syndrome. Methods: To validate the therapeutic potential of iC9.B7-H3 CAR T cells in vivo, NSG mice were orthotopically engrafted with 1x105 patient-derived PDAC6 cells and 9x105 hCAF1 cells at a ratio of 1:9, reflecting a clinically relevant model. In the adjuvant group, mice underwent surgical resection of the primary tumor (distal pancreatectomy and splenectomy) after 25 days. On days 30 and 60, they received systemic iC9.B7-H3 CAR T cell treatment (5x106). In the neoadjuvant group, mice were systemically treated with iC9.B7-H3 CAR T cells on day 19 and underwent surgical resection of the primary tumor on day 25, following another systemic CAR T cell dose on day 60. In the CAR T monotherapy group, mice received systemic iC9.B7-H3 CAR T cells on days 19 and 60. Results: In vivo, iC9.B7-H3 CAR T cells in the neoadjuvant group effectively eradicated both local and distant PDAC metastases for the length of the experiment (180 days) and significantly increased the survival (P &amp;lt;0.0001), indicating long-term efficacy in the treatment of PDAC metastases with no adverse side effects. In the adjuvant and CAR T monotherapy groups, iC9.B7-H3 CAR T cells effectively control tumor growth, eliminate metastases, and significantly increase survival (P=0.0018 and P=0.0007, respectively). Conclusion: These data suggest that the neoadjuvant application of iC9.B7-H3 CAR T cells may demonstrate persistent efficacy in eradicating both local and distant PDAC metastases. iC9.B7-H3 CAR T cells adjuvantly and as monotherapy achieved significant tumor control. Citation Format: Shahrzad Arya, Seyed Amir Sanatkar, Marco Ventin, Giulia Cattaneo, Cristina Martin, Gabriella Lionetto, Jingyu Jia, Feng Chen, David T. Ting, Xinhui Wang, Sandra Ryeom, Cristina R. Ferrone, Soldano Ferrone. Enhancing CAR T cell-based immunotherapy outcomes in PDAC: Evaluating iC9.B7-H3 CAR T cells in adjuvant, neoadjuvant, and monotherapy settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6313.

Abstract 907: ScreenDL: A transfer learning framework integrating tumor omics and functional drug screening for personalized clinical drug response prediction

Abstract Precision oncology hinges on accurate prediction of patient-specific treatment response from tumor molecular inputs. While deep learning (DL) models achieve state-of-the-art response prediction in cell lines, existing methods do not readily translate to the clinic where training data is limited. Here, we have developed and validated ScreenDL, a novel DL framework designed explicitly for use in clinical precision oncology applications. The underlying architecture of ScreenDL consists of two fully connected branches dedicated to learning rich embeddings of a drug’s chemical structure and a tumor’s transcriptomic profile respectively. These tumor omic and drug molecular embeddings are fed into a shared response prediction subnetwork which outputs predicted ln(IC50) values. The ScreenDL training schema incorporates three phases, each designed to improve clinical response prediction: (1) an initial pretraining phase leverages large-scale cell line pharmacogenomic datasets to extract patterns/relationships linking tumor omics and drug response; (2) subsequent transfer learning integrates pharmacogenomic data from patient-derived models of cancer, adapting the pretrained model to a more patient-relevant context; (3) patient-level omics and drug screening data (e.g., from matched patient-derived organoid (PDO) models) is integrated through patient-specific fine-tuning, generating a patient-specific response prediction model. Importantly, biomaterial from surgical tumor resection is often available for organoid establishment and patient-specific drug screening in practical clinical scenarios. To assess the utility of our ScreenDL framework for clinical response prediction, we applied ScreenDL to predict treatment response in 50 advanced/metastatic triple negative breast cancer (TNBC) patient-derived xenograft models (PDX). We leveraged tumor omics profiles for each PDX and drug screening data from matched PDX-derived organoids (PDxOs), mirroring the combination of patient-level tumor omic characterization and functional drug screening in matched PDOs, a protocol currently being piloted in Functional Precision Oncology trials at the University of Utah Huntsman Cancer Institute. After cell line pretraining, ScreenDL achieves a modest median Pearson correlation per drug of 0.15 relative to 0.03 for the leading compared model. However, transfer learning and subsequent PDX-specific fine-tuning significantly improve performance, producing median Pearson correlations per drug of 0.39 and 0.51, respectively. These results demonstrate the ability of our ScreenDL framework to dramatically improve response prediction in clinically relevant domains, bringing DL-based precision treatment selection closer to clinical application. Citation Format: Casey Sederman, Tonya Di Sera, Yi Qiao, Xiaomeng Huang, Bryan E. Welm, Alana L. Welm, Gabor Marth. ScreenDL: A transfer learning framework integrating tumor omics and functional drug screening for personalized clinical drug response prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 907.

Abstract 5091: Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study

Abstract Background: This study aims to investigate the effectiveness of neoadjuvant chemoimmunotherapy (NACI) regimens in treating advanced oral squamous cell carcinoma (OSCC). Methods: We analyzed clinicopathologic features of advanced OSCC patients who received PD-1 inhibitors in combination with carboplatin and paclitaxel before surgical tumor resection between 2020 and 2022. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and pathologic response were used to evaluate the efficacy of the NACI treatment. Adverse events apparently related to NACI treatment were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier survival curves and compared using the log rank test. Additionally, we calculated the area under curve (AUC) to compare the predictive value of PD-L1 expression with baseline serum lipid biomarkers for patient response. Results: Our analysis involved 104 advanced OSCC patients who received NACI. Notably, the top three grade 1-2 treatment-related adverse events (TRAEs) were Alopecia (104; 100%), Anemia (81; 77.9%) and Pruritus (62; 59.6%). Only one patient developed grade 3-4 TRAEs due to increased aminotransferases. The pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. Importantly, patients achieving MPR exhibited higher CPS. The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol (TC) level. Our findings from DFS and OS suggested that patients who underwent NACI before surgery experienced improved survival compared to those who accepted the surgery alone. Conclusions: The data from this study proved evidence that NACI treatment is safe and encouragingly efficacious in treating advanced OSCC patients. Citation Format: Jinsong Li, Bowen Li, Shule Xie, Haotian Cao, Zhaoyu Lin, Qunxing Li, Song Fan. Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5091.