Distant Nodes Research Articles

Abstract PO5-06-03: Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes

Abstract BACKGROUND: Metastatic breast cancer limited to distant lymph nodes is classified as stage IV but potentially represents an anatomically distinct entity amenable to curative treatment. Its optimal management is unclear, with existing studies limited by small sample sizes and short follow-up durations. We sought to investigate the impact of curative-intent treatment on breast cancer-specific survival (BCSS) and overall survival (OS) for patients with this diagnosis. METHODS: Three cohorts of patients diagnosed with breast cancer from 2010 to 2019 were identified from the Surveillance, Epidemiology, and End Results 17 registries database. The curative cohort consisted of patients with metastatic breast cancer involving only distant lymph nodes who received a combination of chemotherapy, surgery to the primary site, and radiotherapy (curative-intent treatment). The palliative cohort included patients who underwent chemotherapy but not curative-intent treatment. The N3c cohort was comprised of patients with ipsilateral supraclavicular lymph node metastases but no distant metastases who received curative-intent treatment. Weighting based on covariate balancing propensity scores was performed to balance age, sex, race, median household income, year of diagnosis, T stage, histology, pathological grade, and ER/PR/HER2 status between the cohorts. Weight-adjusted multivariable Cox regression models with the same covariates were then used to compare the BCSS and OS of the three cohorts. RESULTS: A total of 2,089 patients with a median follow-up of 37 months were eligible for analysis, of whom 577 (27.6%) were in the curative cohort, 905 (43.3%) were in the palliative cohort, and 607 (29.1%) were in the N3c cohort. After propensity score weighting, the maximal standardized mean difference for all covariates was less than 0.1. Five-year BCSS for patients in the weight-adjusted curative, palliative, and N3c cohorts were 63.0% (95% CI 58.1-68.3), 46.7% (42.4-51.4), and 66.4% (61.4-71.8), respectively; and five-year OS were 57.9% (53.0-63.2), 41.2% (37.2-45.7), and 62.2% (57.3-67.6), respectively. Compared to the palliative cohort, the curative cohort exhibited better BCSS (HR 0.47, 95% CI 0.38-0.57; P< 0.001) and OS (HR 0.48, 95% CI 0.40-0.58; P< 0.001). In contrast, the N3c cohort had similar BCSS (HR 0.93, 95% CI 0.73-1.17; P=0.53) and OS (HR 0.96, 95% CI 0.77-1.19; P=0.68) to the curative cohort. CONCLUSIONS: Patients treated curatively for metastatic breast cancer limited to distant lymph nodes had higher BCSS and OS than those receiving palliative chemotherapy and similar BCSS and OS to patients receiving curative-intent treatment for ipsilateral supraclavicular lymph node metastases. These results support the use of aggressive multimodal therapy for select stage IV breast cancer patients with only distant nodal metastases and, if confirmed, suggest that a substantial portion of such patients may be undertreated. Citation Format: Yang Xu. Impact of curative-intent treatment on survival for metastatic breast cancer limited to distant lymph nodes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-03.

Abstract PO5-04-07: Characteristics of patients with metastatic HR+/HER2+ breast cancer in a Kaiser Permanente observational multi-site cohort

Abstract Background: Approximately 10% of female breast cancer and 13% of male breast cancer tumors express hormone-receptor positive/human epidermal growth factor receptor 2 positive (HR+/HER2+) molecular subtype. Since HER2+ targeted agents were made available nearly 10 years ago, there has been limited innovation in treatment of patients with HR+/HER2+ metastatic breast cancer (mBC) to improve clinical outcomes. This study aims to characterize the HR+/HER2+ mBC patient population by describing demographic and clinical characteristics and treatment patterns in a racially diverse, insured, population-based cohort. This study includes data from 4 regions of the Kaiser Permanente (KP) health system – Northwest, Northern California, Southern California, and Colorado. Methods: Eligible study patients were adults age > 18 years with HR+/HER2+ invasive breast cancer who were either initially diagnosed with Stage IV disease or were diagnosed at an earlier stage and experienced recurrence with distant metastasis between 6/8/2012 and 12/31/2019 with data collected through 12/31/2021. Select information was extracted from electronic health records (EHR) of eligible patients and combined with manually abstracted data to create the analytic dataset. Breast cancer recurrence was identified by tumor registrars or obtained through a breast cancer recurrence detection algorithm and verified by chart review. Chart reviewers collected data on metastatic sites, disease progression, reasons for stopping systemic therapy medications, and verified use of medications. Preliminary results: During the study period, we identified 492 subjects with HR+/HER2+ mBC. Seven were men and 485 were women. 221 (45%) had de novo Stage IV breast cancer at diagnosis and 271 (55%) had recurrent mBC. Median age at metastatic diagnosis was 59 years for de novo cases and 62 years for recurrent cases. The cohort was racially and ethnically diverse, with 13% Asian subjects (11% de novo, 15% recurrent), 12% Black subjects (10% de novo, 14% recurrent), and 66% White subjects (71% de novo, 63% recurrent). 18% of cases were recorded as Hispanic (19% de novo, 18% recurrent) in the EHR. Major sites of metastases, including bone, liver, lung, brain, and distant lymph nodes, were similar in both the de novo and recurrent groups. Among women (see table below), 28 (6%) received no systemic treatment for their metastatic disease (9% de novo, 3% recurrent). Among women with systemic treatment, 80% received anti-HER2 agents (90% de novo, 73% recurrent). Of women with recurrent mBC who received systemic therapy, 56% had received anti-HER2 therapy in the adjuvant setting. Conclusion: This population-based study of a racially diverse cohort examined EHR-derived data to describe current demographics and treatment patterns for HR+/HER2+ mBC in an insured patient population. Over 90% of women received systemic therapy, and the majority of those received anti-HER2 therapy per current treatment guidelines. Future analyses will focus on clinical outcomes in this cohort with a goal of informing how prognosis can be improved. Table. Citation Format: Sheila Weinmann, Debra Ritzwoller, Marilyn Kwan, Reina Haque, Stella Stergiopoulos, Ashley Cha, Eric Gauthier, Daniel Sapp, John Dickerson, Kathryn Richert-Boe, Weiming Hu, Nikki Carroll, Lie Hong Chen, Valerie Lee, Ravi Zalavadia, Maureen O'Keeffe-Rosetti. Characteristics of patients with metastatic HR+/HER2+ breast cancer in a Kaiser Permanente observational multi-site cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-07.

Abstract PO3-22-12: Clinical feasibility of nipple sparing mastectomy (NSM) followed by immediate reconstruction based on direct-to-implant technique

Abstract [Background] The development of NSM approach combined with immediate implant-based breast reconstruction (IBBR) for patients with earlystage breast cancer (BC) preserve the natural skin envelope including nipple-areolar complex (NAC) to able to immediately reconstruct the breast with a permanent implant and simultaneously omit the skin expansion with a tissue expander. We retrospectively analyzed the clinical results of NSM+IBBR and compared the complication rate, outcome of patients who underwent immediate (one-stage) or delayed (two-stage) IBBR followed by standard TM or NSM. [Patients and Results] A total of 108 patients who underwent a TM that included SSM or NSM followed by one- or two-stage IBBR between January 2013 and April 2022. 53 patients underwent a total mastectomy (TM) and 32 patients underwent an NSM followed by two-stage IBBR, and 24 patients underwent an NSM followed by one-stage IBBR. The operation times were 236, 247.2, and 321 min, and the mean surgical bleeding was 60.4, 88.8, and 138 ml, respectively. The complications in the three groups included infection (2.7%, 11.1%, and 6.3%), seroma/hematoma (0%, 5.6%, and 6.3%), flap necrosis (2.7%, 11.1%, and 12.5%), and loss of tissue expander or implant (2.7%, 5.6%, and 6.3%), respectively. At the median 62-month follow-up after the NSM + IBBR, one patient was diagnosed with distant lymph node metastases at the 24-month follow-up and one patient had new primary breast cancer within the reconstructed breast at the 38-month follow-up. But no loco-regional recurrence at the NAC or other distant recurrence were detected in the patients undergone regardless TM or NSM + one-stage or two-stage IBBR. [Summary] Our results suggested that the use of one-stage IBRR tended to increase the operating time and the amount of bleeding compared to two-stage IBRR and the complication rate might be higher in cases in which an NSM is followed by IBBR. Oncological outcome was consistent with the studies showing that loco-regional recurrence is less likely at the NAC regardless of whether the patients underwent one-stage or two-stage IBBR following an NSM. Citation Format: Uhi Toh, Yuko Takao, Yuriko Katagiri, Rie Sugihara, Hidetaka Watanabe. Clinical feasibility of nipple sparing mastectomy (NSM) followed by immediate reconstruction based on direct-to-implant technique [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-12.

Abstract PO4-05-08: Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China

Abstract Background: Endocrine therapy resistance was classifed as primary and secondary, guiding the first-line (1L) treatment choices for hormone receptor positive, HER2-negative (HR+/Her2-) metastatic breast cancer (mBC). However, it is unknown whether it is primary ET resistance or not to the stage IV de novo patients. Therefore, We performed a retrospective study to predict primary resistance in advance in de novo patients and have a more appropriate treatment strategy. Methods: We identified newly diagnosed with stage IV de novo HR+/HER2- mBC patients received single-agent endocrine therapy (ET) or ET plus CDK4/6 inhibitors (CDK4/6i) in 1L setting from January 1, 2020 to Jun 30, 2022, using the National Cancer Information Database (NCID) in China. Primary ET resistance (PER) was defined as switching to second-line treatment within 6 months after receiving the 1L ET±CDK4/6i, whereas secondary ET resistance (SER) patients were those who received 1L ET±CDK4/6i treatment more than six months. The Chi-Square test was used to compare the baseline characteristics of PER and SER patients. Result: A total of 217 patients who met the inclusion criteria were included in the analysis, among which 161 patients received single-agent ET and 56 patients received ET plus CDK4/6i. 18.4% of the patients were classified as PER patients, whereas 81.6% showed SER patients. PER patients were younger (median age of 52 years vs. 58 years in SER patients, p=0.01). In terms of clinicopathological characteristics, patients with PER have a higher percentage of liver metastases (14/40 (35%) vs. 20/177 (11.3%) in SER, p< 0.01), distant lymph node metastases (19/40 (34%) vs. 45/177 (25.4%) in SER, p = 0.01), and bone metastases (30/40(75%) vs. 97/177(54.8%) in SER, p = 0.02). Furthermore, the PER rate was 21.7% (35/161) in patients received single-agent ET, compare with 8.9% (5/56) in ET plus CDK4/6i patients, p=0.04. Regarding the following treatment pattern in the PER patients, a high percentage of patients received chemotherapy, accounting for 50%, 30% still received another endocrine therapy, and the remaining 20% patients received CDK4/6i combined with endocrine therapy. Conclusions: There is still a significant proportion of de novo HR+/HER2- mBC patients with primary endocrine resistance, a relatively low proportion of PER in patients receiving endocrine in combination with CDK4/6i. Table. The proportion of primary endocrine resistance across treatment regimens in de novo HR+/HER2- metastatic breast Cancer Citation Format: Zhanhong Chen, Xiying Shao, Yabing Zheng, Wenming Cao, Junqing Chen, Weizhu Wu, Ting Wang, Xiaojia Wang. Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-08.

S1‐Leitlinie Talgdrüsenkarzinom

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable or metastatic sebaceous gland carcinomas. Local procedures and system therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually in an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

Conversion surgery for gastric remnant cancer with liver metastasis after nivolumab combination chemotherapy achieving pathological complete response: a case report and literature review.

Nivolumab combination chemotherapy has recently emerged as a potential first-line treatment for patients with unresectable or metastatic gastric cancer (GC). Further research has indicated that R0 resection by conversion surgery could be an effective treatment strategy to improve overall survival. However, there have been limited reports on the successful application of conversion surgery following combination chemotherapy achieving pathological complete response (pCR) in cases of advanced gastric remnant cancer with liver metastasis. Here, we present a case of long-term survival in a patient who underwent this treatment. A 54-year-old man was initially referred to our department for treatment of stage III (cT3N1M0) gastric cancer where he underwent laparoscopic distal gastrectomy and D2 lymph node dissection. After a year of uneventful follow-up, the patient was diagnosed with a tumor in the gastric remnant combined with liver metastasis, resulting in a diagnosis of stage IV (cT3N0M1) gastric remnant cancer. Subsequently, the patient was treated with four cycles of TS-1, Oxaliplatin, and Nivolumab as the first-line regimen. Remarkably, both the remnant tumor and liver metastasis exhibited significant shrinkage, and no new lesions were found. Given this response, conversion surgery was performed to achieve complete resection of the remnant gastric cancer and liver metastasis, followed by laparoscopic remnant gastrectomy and partial hepatectomy. Pathological examination revealed the absence of residual carcinoma cells and lymph node metastases. Postoperatively, the patient was treated with adjuvant chemotherapy with S-1 for 1 year, and survived without recurrence for 18months after conversion surgery. Nivolumab combination chemotherapy shows promise as a clinically beneficial treatment approach for gastric remnant cancer with liver metastasis, particularly when pCR can be achieved following conversion surgery.

A graph-based approach for traffic prediction using similarity and causal relations between nodes

Accurate traffic prediction is crucial for the development of intelligent transportation systems (ITS) and various smart applications. To achieve this, effectively capturing the complex interplay between spatial and temporal dependencies across traffic nodes is essential. However, existing research often focuses solely on fixed spatial dependencies between neighboring nodes, neglecting the potential influence of distant nodes. This paper addresses these limitations by exploring two key types of relationships among traffic nodes. First, we examine indirect relationships based on similarity, where nodes exhibit similar traffic patterns irrespective of their physical proximity. Second, we investigate direct causal relationships, where traffic conditions at one node are directly influenced by other nodes. Based on these findings, we propose a novel approach named TPSC (Traffic Prediction using nodes Similarity and Causal relations). TPSC incorporates a classifier that utilizes the K-Prototype algorithm to group nodes based on their traffic similarity and nearby points of interest (POIs). Separate models are then trained for each cluster. Our model leverages a spatial module that employs graph convolutional network representation learning alongside transfer entropy to capture causal relationships and dynamic spatial dependencies. Additionally, a temporal module is introduced to capture periodic temporal dependencies across three components: recent patterns, daily patterns, and weekly patterns. Extensive experiments are conducted to evaluate proposed model on four large-scale traffic datasets for multiple traffic characteristics including speed, flow, and travel time. The experimental results demonstrate that TPSC surpasses the performance of the compared baselines, highlighting its superior predictive capabilities in traffic prediction.

S1-Guideline Sebaceous Carcinoma.

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

Joint computational and optimized resource allocation in edge computing networks

Fog computing has several undeniable benefits, such as enhancing near-real-time response, reducing transmission costs, and facilitating IoT analysis. This technology is poised to have a significant impact on businesses, organizations, and our daily lives. However, mobile user equipment struggles to handle the complex computing tasks associated with modern applications due to its limited processing power and battery life. Edge computing has emerged as a solution to this problem by relocating processing to nodes at the network’s periphery, which have more computational capacity. With the rapid evolution of wireless technologies and infrastructure, edge computing has become increasingly popular. Nevertheless, managing fog computing resources remains challenging due to resource constraints, heterogeneity, and distant nodes. For delay-sensitive intelligent IoT applications within the fog computing architecture, cooperation and communication processing resources in 6 G and future networks are essential. This study proposes a joint computational and optimized resource allocation (JCORA) technique to accelerate the processing of data from intelligent IoT sensors in a cell association environment. The proposed technique utilizes an uplink and downlink power allocation factor and the shortest job first (SJF) task scheduling system to optimize user fairness and decrease data processing time. This is a complex assignment due to several non-convex limitations. The suggested JCORA-SJF model simultaneously optimizes time partitioning, computing task processing mode selection, and target sensing location selection to maximize the weighted total of task processing and communication performance. The simulation results demonstrate the effectiveness of the proposed JCORA-SJF algorithms, and the system’s scalability is also examined.

Supervised contrastive learning for graph representation enhancement

Graph Neural Networks (GNNs) have exhibited significant success in various applications, but they face challenges when labeled nodes are limited. A novel self-supervised learning paradigm has emerged, enabling GNN training without labeled nodes and even surpassing GNNs with limited labeled data. However, self-supervised methods lack class-discriminative node representations due to the absence of labeled information during training. In this paper, we exploit a supervised graph contrastive learning approach (SGCL) framework to tackle the issue of limited labeled nodes, ensuring coherent grouping of nodes within the same class. We propose augmentation techniques based on a novel centrality function to highlight important topological structures. Additionally, we introduce a supervised contrastive learning method that removes the necessity for negative samples and simplifies complex elements effortlessly. Our approach combines supervised contrastive loss and node similarity regularization while achieving consistent grouping of unlabeled nodes with labeled ones. Furthermore, we utilize the pseudo-labeling technique to propagate label information to distant nodes and address the underfitting problem, especially with low-degree nodes. Experimental results on real-world graphs demonstrate that SGCL outperforms both semi-supervised and self-supervised methods in node classification.

Novel GCN Model Using Dense Connection and Attention Mechanism for Text Classification

Convolutional Neural Network (CNN) or Recurrent Neural Network (RNN) based text classification algorithms currently in use can successfully extract local textual features but disregard global data. Due to its ability to understand complex text structures and maintain global information, Graph Neural Network (GNN) has demonstrated considerable promise in text classification. However, most of the GNN text classification models in use presently are typically shallow, unable to capture long-distance node information and reflect the various scale features of the text (such as words, phrases, etc.). All of which will negatively impact the performance of the final classification. A novel Graph Convolutional Neural Network (GCN) with dense connections and an attention mechanism for text classification is proposed to address these constraints. By increasing the depth of GCN, the densely connected graph convolutional network (DC-GCN) gathers information about distant nodes. The DC-GCN multiplexes the small-scale features of shallow layers and produces different scale features through dense connections. To combine features and determine their relative importance, an attention mechanism is finally added. Experiment results on four benchmark datasets demonstrate that our model’s classification accuracy greatly outpaces that of the conventional deep learning text classification model. Our model performs exceptionally well when compared to other text categorization GCN algorithms.

Two cases of gastric cancer with elevated serum levels of KL-6

BackgroundThe serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6.Case presentationThe first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml.ConclusionsThese two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases.

CD146 Promotes EMT-Mediated Migration and Invasion of NSCLC via PI3K/Akt Signaling Pathway.

Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer.

Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

Potential for Metastasis and Recurrence in Colorectal Carcinoma In Situ: A Retrospective Analysis of 1069 Patients

BackgroundColorectal carcinoma in situ, characterized by cancer limited to the intramucosal layer or known as intraepithelial carcinoma, has conventionally considered to be without any risk of regional lymph node metastasis. However, isolated cases of regional lymph node metastasis, local recurrence, and distant metastasis challenge this assumption. This study aimed to assess the occurrence of regional lymph node metastasis and recurrence of colorectal carcinoma in situ. MethodsA retrospective analysis was conducted in 1069 patients who underwent full-thickness local excision or radical surgery for colorectal carcinoma in situ between January 1994 and December 2020. Histopathological features were assessed by two experienced pathologists. In cases of suspected recurrence, evaluation involved abdomen-pelvis and chest computed tomography, or PET-CT. ResultsThe recurrence rate of Tis patients was 0.46%. Among the patients, 9 were diagnosed with regional lymph node metastasis or cancer recurrence. Of these, 4 patients were diagnosed with lymph node metastasis during primary surgery; 2 exhibited regional lymph node metastasis, and 2 presented with both regional and distant lymph node metastases. Regional lymph node metastasis occurred in additional 2 patients after radical surgery for the primary tumor. Distant metastasis was observed in 3 patients: hepatic metastasis in one, hepatic and pulmonary metastases in another, and small bowel metastasis in the third patient. Among the 5 patients experiencing cancer recurrence, 1 expired due to cancer progression. ConclusionContrary to previous assumptions, colorectal carcinoma in situ can potentially metastasize to lymph nodes and recur. Therefore, careful assessment at the time of diagnosis is crucial, recognizing the possibility of lymph node metastasis or recurrence. This approach is essential for accurately identifying instances of cancer recurrence and ensuring optimal oncological outcomes.Microabstract: Among the 1069 patients diagnosed with carcinoma in situ colorectal cancer, 9 were diagnosed with regional lymph node metastasis or cancer recurrence and distant metastasis was observed in 3 patients. Such vigilance is imperative to accurately detect any recurrence of the cancer and to achieve the best possible oncological outcomes.

Optical gain in a degenerate two-level system in the presence of a transverse magnetic field

Here we report a theoretical model that allows magnetically assisted narrowband probe beam amplification in a closed two-level system with triple Zeeman degeneracy. The gain mechanism can be understood in terms of coherent population transfer between the levels of the Zeeman ground state induced by the external magnetic field. The theoretical model we develop here using a simpler atomic transition Fg=1→Fe=0, in agreement with the experimental results already observed in recent literature. Additionally, we validate our theoretical predictions with the results obtained via density matrix numeric calculation and we believe our theoretical results could useful in communication protocols involving distant nodes.

Adaptive Mobile Recharge Scheduling With Rapid Data Sharing in Wireless Rechargeable Networks

The recent breakthrough in Wireless Power Transfer (WPT) provides a promising way to prolong network lifetime by employing a charging vehicle to replenish energy. Data transmissions from nodes typically happen in response to physical sensory events, leading to time-varying energy consumption. To improve charging efficiency, the existing schemes collect energy information by employing a data-gathering vehicle or data collection protocol. However, in duty cycle networks, these schemes either incur extra vehicles or high data collection delay. To solve this problem, we propose an mobile adaptive charging scheme with rapid data sharing (rShare), which establishes multi-layer collection trees and collects overall energy data to the vehicle. A spatial predicted active sending (SPAS) algorithm is proposed for distant nodes to actively estimate the future position and transmit their data to cover potential positions of the charging vehicle, which significantly reduces data collection delay. We also propose an estimated time of arrival (ETA)-aware scheme based on the TSP Nearest Neighbor algorithm that updates the charging path based on the collected data. Extensive simulation results demonstrate that our scheme outperforms the state-of-the-arts in terms of dead node avoidance with less communication overhead.

Sliding limited penetrable visibility graph for establishing complex network from time series.

This study proposes a novel network modeling approach, called sliding window limited penetrable visibility graph (SLPVG), for transforming time series into networks. SLPVG takes into account the dynamic nature of time series, which is often affected by noise disturbances, and the fact that most nodes are not directly connected to distant nodes. By analyzing the degree distribution of different types of time series, SLPVG accurately captures the dynamic characteristics of time series with low computational complexity. In this study, the authors apply SLPVG for the first time to diagnose compensation capacitor faults in jointless track circuits. By combining the fault characteristics of compensation capacitors with network topological indicators, the authors find that the betweenness centrality reflects the fault status of the compensation capacitors clearly and accurately. Experimental results demonstrate that the proposed model achieves a high accuracy rate of 99.1% in identifying compensation capacitor faults. The SLPVG model provides a simple and efficient tool for studying the dynamics of long time series and offers a new perspective for diagnosing compensation capacitor faults in jointless track circuits. It holds practical significance in advancing related research fields.

Transitivity-Preserving Graph Representation Learning for Bridging Local Connectivity and Role-Based Similarity

Graph representation learning (GRL) methods, such as graph neural networks and graph transformer models, have been successfully used to analyze graph-structured data, mainly focusing on node classification and link prediction tasks. However, the existing studies mostly only consider local connectivity while ignoring long-range connectivity and the roles of nodes. In this paper, we propose Unified Graph Transformer Networks (UGT) that effectively integrate local and global structural information into fixed-length vector representations. First, UGT learns local structure by identifying the local sub-structures and aggregating features of the k-hop neighborhoods of each node. Second, we construct virtual edges, bridging distant nodes with structural similarity to capture the long-range dependencies. Third, UGT learns unified representations through self-attention, encoding structural distance and p-step transition probability between node pairs. Furthermore, we propose a self-supervised learning task that effectively learns transition probability to fuse local and global structural features, which could then be transferred to other downstream tasks. Experimental results on real-world benchmark datasets over various downstream tasks showed that UGT significantly outperformed baselines that consist of state-of-the-art models. In addition, UGT reaches the third-order Weisfeiler-Lehman power to distinguish non-isomorphic graph pairs.

Abstract 3977: Neoadjuvant chemotherapy and radiation shape the local and regional adaptive antitumor immune response in lung squamous cell carcinomas

Abstract Chemotherapy (CT) and radiotherapy (RT) are known for their stimulating as well as inhibiting effects on the anti-tumor immune response. This study aimed to understand how CT and RT change the local immune microenvironment of the tumor and the regional immune response in draining lymph nodes. Evaluations were performed on lung squamous cell carcinomas (LUSC) with a special focus on tertiary lymphoid structures (TLS) and lymph follicles. A cohort of 21 untreated LUSC (naiveLUSC) and 21 matched neoadjuvantly treated LUSC (neoLUSC) was compiled. Digitized H&amp;E whole slide images of the tumor and of two representative probes of a proximal and distal lymph node were assessed. A pathologist blinded to the groups assigned tumors to one of three immunophenotypes (inflamed, excluded, desert) by visual analysis. Tertiary lymphoid structures (TLS) in the tumor area and lymph follicles in the regional lymph nodes were counted and characterized according to their maturation status (with/without germinal center). RNAseq analyses were performed for a subset of tumors. NeoLUSC tended to more frequently have a desert immune phenotype (6/21 versus 1/21, p=0.0931). The mean number of TLS was significantly reduced in neoLUSC compared to naiveLUSC (4 versus 9, p=0.0179). Additionally, neoLUSC had a significantly lower likelihood for the presence of mature TLS with germinal centers (3/21 versus 9/21, p=0.0327). While the mean number of lymph follicles in regional lymph nodes was comparable between neoLUSC and naiveLUSC, neoLUSC had a significantly reduced number of mature lymph follicles (20% versus 41% of lymph follicles, p=0.0376) in distant lymph nodes and showed a similar, but less pronounced trend in proximal lymph nodes. In general, the amount of TLS correlated with the amount of lymph follicles in naiveLUSC patients (p=0.0154), but not in neoLUSC patients. Across the complete cohort, long-term survivors (&amp;gt;2 years) tended to have higher numbers of lymph follicles in lymph nodes than short term survivors (1.6 versus 1.1 lymph follicles/mm2, p=0.0805). RNAseq analysis revealed a significant upregulation of inflammatory gene sets and downregulation of cell cycle associated gene sets in neoLUSC as compared to naiveLUSC. This study demonstrates that CT and RT are potent, but multimodal influencers of the local tumor immune microenvironment as well as the regional immune response of the draining lymph nodes. While gene expression results underline the inflammation promoting effect of CT and RT, histological evaluations suggest that CT and RT negatively affect the adaptive anti-tumor immune response by reducing the development and maturation of TLS and lymph follicles in the lymph nodes. Next steps include an artificial intelligence based cell characterization and spatial evaluation of the tumor immune microenvironment to further unveil functional changes induced by CT and RT. Citation Format: Rosemarie Krupar, Justin Nieder, Johannes Braegelmann, Mareike Haarmann, Torsten Goldmann, Sharon Ruane, Timo Milbich, Cornelius Boehm, Lukas Ruff, Julika Ribbat-Idel, Christian Watermann, Sven Perner, Christiane Kuempers. Neoadjuvant chemotherapy and radiation shape the local and regional adaptive antitumor immune response in lung squamous cell carcinomas [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 3977.