Distant Nodes Research Articles

Surveillance of prognostic risk factors in patients with SCCB using artificial intelligence: a retrospective study

Small cell carcinoma of the bladder (SCCB) is a rare urological tumor. The prognosis of SCCB is abysmal. Therefore, this study aimed to construct nomograms that predict overall survival (OS) and cancer-specific survival (CSS) in SCCB patients. Information on patients diagnosed with SCCB during 2004–2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models analyzed Independent risk factors affecting patients' OS and CSS. Nomograms predicting the OS and CSS were constructed based on the multivariate Cox regression model results. The calibration curve verified the accuracy and reliability of the nomograms, the concordance index (C-index), and the area under the curve (AUC). Decision curve analysis (DCA) assessed the potential clinical value. 975 patients were included in the training set (N = 687) and the validation set (N = 288). Multivariate COX regression models showed that age, marital status, AJCC stage, T stage, M stage, surgical approach, chemotherapy, tumor size, and lung metastasis were independent risk factors affecting the patients' OS. However, distant lymph node metastasis instead AJCC stage is the independent risk factor affecting the CSS in the patients. We successfully constructed nomograms that predict the OS and CSS for SCCB patients. The C index of the training set and the validation set of the OS were 0.747 (95% CI 0.725–0.769) and 0.765 (95% CI 0.736–0.794), respectively. The C index of the CSS were 0.749 (95% CI 0.710–0.773) and 0.786 (95% CI 0.755–0.817), respectively, indicating that the predictive models of the nomograms have excellent discriminative power. The calibration curve and the AUC also show good accuracy and discrimination of the nomograms. To sum up, We established nomograms to predict the OS and CSS of SCCB patients. The nomograms have undergone internal cross-validation and show good accuracy and reliability. The DCA shows that the nomograms have an excellent clinical value that can help doctors make clinical-assisted decision-making.

MEAI: an artificial intelligence platform for predicting distant and lymph node metastases directly from primary breast cancer.

Breast cancer patients typically have decent prognoses, with a 5-year survival rate of more than 90%, but when the disease metastases to lymph node or distant, the prognosis drastically declines. Therefore, it is essential for future treatment and patient survival to quickly and accurately identify tumor metastasis in patients. An artificial intelligence system was developed to recognize lymph node and distant tumor metastases on whole-slide images (WSIs) of primary breast cancer. In this study, a total of 832 WSIs from 520 patients without tumor metastases and 312 patients with breast cancer metastases (including lymph node, bone, lung, liver, and other) were gathered. Based on the WSIs were randomly divided into the training and testing cohorts, a brand-new artificial intelligence system called MEAI was built to identify lymph node and distant metastases in primary breast cancer. The final AI system attained an area under the receiver operating characteristic curve of 0.934 in a test set of 187 patients. In addition, the potential for AI system to increase the precision, consistency, and effectiveness of tumor metastasis detection in patients with breast cancer was highlighted by the AI's achievement of an AUROC higher than the average of six board-certified pathologists (AUROC 0.811) in a retrospective pathologist evaluation. The proposed MEAI system can provide a non-invasive approach to assess the metastatic probability of patients with primary breast cancer.

Excitatory-inhibitory mismatch shapes node recruitment in an epileptic network.

Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood. We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy-1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike-triggered coactivity maps. Experiments were repeated with 4-aminopyridine as an epileptic agent. We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node-specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy-1 excitatory cells were more heavily recruited. Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell-specific dynamics in the spatial propagation of epileptiform activity.

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

BackgroundAlthough immunotherapy greatly extends overall survival (OS) of patients with extensive-stage small cell lung cancer (ES-SCLC), a number of patients develop immunotherapy resistance (IR). Patterns of failure in ES-SCLC are not clarified. Our study aims to explore the clinical pattern of IR and prognostic factors for these patients. MethodsThe study was conducted from 117 ES-SCLC patients with immunotherapy between 2018 and 2022. Chi-square tests and Fishers' exact tests was used to explore failure patterns in different populations. Survival analyses of different progression patterns and subsequent treatment regimens were conducted by Kaplan–Meier curves and log-rank test. Results86 (73.5%) patients experienced IR. The patients with smoking (never smoker vs. current or ex-smoker, 59.5 % vs. 81.3%, P = 0.010), liver metastasis (extrahepatic metastasis vs. intrahepatic metastasis, 73.6 % vs. 90.9%, P = 0.050), and distant metastasis status (no distant metastasis vs. distant metastasis, 39.1 % vs. 81.9%, P<0.001) were associated with IR rates. Liver progression had a lower incidence in 1st line immunotherapy (1st line vs. ≥2nd lines, 14.0 % vs. 41.7%, P = 0.004) and a higher incidence in multiple progression (multiple progression vs. Oligo-progression, 39.4 % vs. 17.0%, P = 0.021). Cranial (41.7 % vs. 16.1%, P = 0.012) and distant lymph node (16.7 % vs. 3.2%, P = 0.049) progression were the main failure model for acquired IR in comparison to primary IR. Patients with new lesion progression only (17.73 vs. 9.17 months, P = 0.013) and non-hepatic progression (14.23 vs. 11.67 months, P = 0.042) had a longer OS. Patients in cross-line immunotherapy after IR had a favourable prognosis (17.07 vs. 11.93 months, P = 0.007). ConclusionThe most common failure pattern of immunotherapy for ES-SCLC was lung and regional lymph node progression. Brain and liver progression were the most common extra thoracic failure sites for 1st line and 2nd and more lines immunotherapy, respectively. There was a higher probability of primary IR in 2 lines and above immunotherapy. Patients with new only progression site and cross-line rechallenge immunotherapy had a better prognosis.

Hertz-rate metropolitan quantum teleportation

Quantum teleportation can transfer an unknown quantum state between distant quantum nodes, which holds great promise in enabling large-scale quantum networks. To advance the full potential of quantum teleportation, quantum states must be faithfully transferred at a high rate over long distance. Despite recent impressive advances, a high-rate quantum teleportation system across metropolitan fiber networks is extremely desired. Here, we demonstrate a quantum teleportation system which transfers quantum states carried by independent photons at a rate of 7.1 ± 0.4 Hz over 64-km-long fiber channel. An average single-photon fidelity of ≥90.6 ± 2.6% is achieved, which exceeds the maximum fidelity of 2/3 in classical regime. Our result marks an important milestone towards quantum networks and opens the door to exploring quantum entanglement based informatic applications for the future quantum internet.

O141 The patterns of metastatic disease and survival in patients with pancreatic neuroendocrine tumours: a retrospective observational study

Abstract Background The 5-year survival of patients with pancreatic neuroendocrine tumours (pNET) without metastatic spread can be as high as 93% and as low as 24% in cases with distant metastases, influenced by the resectability of the tumour and adjuvant therapies. This study examined the patterns of metastasis and survival outcomes of patients with pNET. Methods This retrospective observational study at a regional hepatopancreaticobiliary centre, used electronic healthcare records to identify all patients with confirmed pNET referred to the multidisciplinary team between 2010 and 2019. Demographic characteristics of the patients were compared using chi-squared testing, and the patterns of metastatic disease defined on radiological imaging. The 5-year survival outcomes were determined using Kaplan-Meier survival estimates, stratified by the presence (and location) or absence of metastatic disease. Results In total 96 [50 (52.1%) female] patients with pNET were identified. Of the female patients, 46% were older than 70-years compared with 24% of the males (p=0.016). Metastatic disease was present in 48% of patients at presentation. The commonest sites of metastases was the liver (50%) distant lymph node metastases (32%) and multisite metastases (13%). The corresponding 5-year survivals were 58%, 50% and 39%. Conclusion pNET is a unique type of pancreatic cancer with better overall survival compared with other pancreatic cancers. Survival is influenced by the patterns of metastatic disease with worse overall survival in those with multisite metastases.

Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study

Background/PurposeThe present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and MethodsThis retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. ResultsThe median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64–3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023–1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139–0.826, p = 0.017) remained significant. ConclusionTo our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.

Subcapsular sinus macrophage infection after viral dissemination to distal lymph nodes maximizes germinal center responses

Abstract Neutralizing antibodies are a hallmark of protective humoral response against many viral infections. Microanatomical structures called germinal centers (GCs) within the secondary lymphoid organs are the sites where B cells get differentiated into high affinity antibody secreting, class switched and long-lasting plasma and memory B cells. Most studies of antigen movement leading to B cell activation have been performed using subcutaneous injection, mimicking the natural route of infection. Under this condition, virus infects sinusoidal lymph node macrophages which relay the antigen to B cells to drive the GC responses. However, not much is known about antigen movement during the generation of GCs in the non-draining (or distal lymph nodes) after systemic viral dissemination. Using ZIKV infection of mice, we have mapped virus dissemination through two separate lymph node chains. Surprisingly, GCs efficiently formed in distal LNs, although with delayed kinetics compared to those directly draining the infection site. Remarkably, virus in the blood alone was not sufficient to produce GCs. Instead, virus still reached the LNs through the lymphatics and infected LN sinusoidal macrophages. This coincided with virus-induced vascular permeability in the tissue. Thus, GC formation still proceeds through sinusoidal LN macrophages even when virus is spread through the blood. Our findings reveal a conserved mechanism for antiviral B cell development in LNs distal from the site of infection.

Exploiting potentialities for space-based quantum communication network: downlink quantum key distribution modelling and scheduling analysis

The goal of the space-based quantum network is to form the backbone of the quantum internet for long-distance secure data transfer, networked distributed quantum information processing, and other applications. Consider that the quantum network evolved from a recent form where a satellite performs a sequence of satellite-to-ground quantum key distribution (SatQKD) missions that allow any two ground nodes to have the symmetric encryption keys, we here develop a framework for the SatQKD downlink modelling and scheduling analysis. Incorporated with the orbital calculation and the meteorological data to downlink SatQKD modelling, the dynamic characteristics of the satellite-to-ground optical transmission could be simulated. Our work shows that the satellite downlink scheduling allows for the possibility to consider different strategies for SatQKD missions such as extending connection for distant ground nodes, prioritized delivery and promoting keys utilization, which may guide design and analysis of future missions for future satellite application.

Primary Bone Lymphoma of the Knee: A Rare Entity

Introduction: The World Health Organization (WHO) defined primary bone lymphoma as a single bone lesion with or without regional lymph node involvement or multiple bone lesions without distant visceral or lymph node involvement. It is a rare entity; indeed, primary bone lymphomas represent 1-3% of non-Hodgkin's lymphomas, 5% of extra-nodal non-Hodgkin's lymphomas and 3% of primary bone tumors [2, 3]. Objective: The objective of our work is to clarify the imaging of a rare entity of primary bone lymphoma in a 6-year-old boy, who had been complaining for 1 month of pain in his right lower limb without functional impotence. Case Report: A 6 year old boy, who had been complaining for 1 month of pain in his right lower limb without functional impotence or other associated signs. The clinical examination revealed a child in good general condition, apyretic, with a limp when walking, limitation of all the articular amplitudes of the left he knee, a swelling of the homolateral thigh with discreet quadricipital amyotrophy. Examination of the lymph nodes did not identify any adenopathies. Standard radiographs of the left knee showed multiple lesions involving the lower extremities of the femur and the upper extremities of the tibia, with confluent intraspongiosa and areas of osteocondensation associated with localized cortical fracture without periosteal reaction. The biological workup revealed no abnormalities, including an LDH in the normal range. An MRI of the right thigh was requested for a better characterization of the lesion and to establish a locoregional extension assessment. It showed a large epiphyseal-metaphyseal lesion process of the lower end of the femur and epiphyseal-metaphyseal of the upper end of the left tibia in T1 hyposignal, locally infiltrating T2 heterogeneous hyper signal with vascular enclosure and popliteal ADPs. The CT scan was requested as part of the extension work-up and did not reveal any secondary lesion. The patient underwent a bone ........

Ex vivo intranodal administration of sirolimus

BackgroundImmune-mediated adverse effects of current systemic immunosuppression therapy compromise long-term survival of liver transplant recipients. Our recently observed results showed that intranodal delivery of sirolimus induced interleukin (IL)-10–driven CD4+ CD25+ Foxp3+ regulatory T cells. The present report investigated the feasibility of intra-nodal delivery of sirolimus ex vivo into a human liver common bile duct lymph node. MethodsWe used a discarded donor human liver to directly administer sirolimus into a distal common bile duct lymph node. Sirolimus was injected once using an ultrasound-guided method. ResultsThe porta hepatis and its lymph node along the distal common bile duct were exposed. A handheld ultrasound probe (L15-7io, Koninklijke Philips N.V.) with a layer of standoff Aquasonic 100 Ultrasound Transmission Gel (Parker Laboratories, Inc) was applied to the exposed lymph node. Using a 1.0-mL 25G hypodermic needle, 0.05 mL of sirolimus solution was injected directly into the exposed lymph node. ConclusionsUnder sonographic guidance, direct injection of sirolimus into a hepatic draining lymph node along the common bile duct is accomplished precisely and reliably. Direct administration of therapeutic agents into local lymph nodes is a viable approach for effective targeted immunotherapy.

Immune Checkpoint Inhibitor, Nivolumab, Combined with Chemotherapy Improved the Survival of Unresectable Advanced and Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Experience.

Patients with advanced esophageal squamous cell carcinoma (SCC) have a poor prognosis when treated with standard chemotherapy. Programmed death ligand 1 (PD-L1) expression in esophageal cancer has been associated with poor survival and more advanced stage. Immune checkpoint inhibitors, such as PD-1 inhibitors, showed benefits in advanced esophageal cancer in clinical trials. We analyzed the prognosis of patients with unresectable esophageal SCC who received nivolumab with chemotherapy, dual immunotherapy (nivolumab and ipilimumab), or chemotherapy with or without radiotherapy. Patients who received nivolumab with chemotherapy had a better overall response rate (ORR) (72% vs. 66.67%, p = 0.038) and longer overall survival (OS) (median OS: 609 days vs. 392 days, p = 0.04) than those who received chemotherapy with or without radiotherapy. In patients receiving nivolumab with chemotherapy, the duration of the treatment response was similar regardless of the treatment line they received. According to clinical parameters, liver and distant lymph nodes metastasis showed a trend of negative and positive impacts, respectively, on treatment response in the whole cohort and in the immunotherapy-containing regimen cohort. Nivolumab add-on treatment showed less gastrointestinal and hematological adverse effects, compare with chemotherapy. Here, we showed that nivolumab combined with chemotherapy is a better choice for patients with unresectable esophageal SCC.

Abstract 3537: A novel orthotopic xenograft model of spontaneous metastasis for rhabdomyosarcoma using lingual intramuscular injection

Abstract Rhabdomyosarcoma (RMS), a cancer characterized by the defective differentiation of skeletal muscle precursor cells, is the most common pediatric soft tissue sarcoma. Despite significant efforts to characterize the transcriptomic and genetic abnormalities of the disease, the prognosis for patients with advanced or refractory disease has remained unchanged for more than four decades. Preclinically, studies have been hampered by insufficient animal models. For example, the hindlimb orthotopic model, an injection into the gastrocnemius muscle of immunocompromised mice, produces highly encapsulated, non-invasive, non-metastatic tumors. While this model has shown a reasonable recapitulation of tumor proliferation response, investigators using this model are unable to assess the effect of their investigational treatment on local invasion or distant metastasis. Moreover, transgenic mouse models of RMS, while commonly metastatic, diverge significantly from the transcriptomic signature of human tumors. With these considerations, we hypothesized that an alternative orthotopic site, the tongue, may provide a more representative xenograft model of RMS. In a proof of principal experiment, the fusion negative RMS (FN-RMS) cell line RD was injected into the skeletal muscle of the tongue, a lingual intramuscular (LIM) injection. Tongue tumors establish in approximately 60-80% of mice injected within approximately 40 days. By histopathology, the primary tumors show evidence of local invasion. Interestingly, approximately 60% of these tumors also spread to local cervical lymph nodes, a process not observed in hindlimb orthotopic models or subcutaneous models. We expanded our investigation to include additional FN-RMS cell lines: RMS-YM, SMS-CTR, and a MEK inhibitor resistant cell line CTR-557. Mice injected with RMS-YM cells established tumors in at least 60% of mice by 75 days post injection. Additionally, enlarged local and distant lymph nodes are observed in 50% of these mice. Intriguingly, mice injected with SMS-CTR or its MEK inhibitor resistant derivative, CTR-557, frequently have tumors in both local and distant lymph nodes without evidence of a primary tongue tumor. One mouse in each group also had pulmonary metastases. Taken together, this model not only demonstrates the first orthotopic xenograft model of spontaneous metastasis for FN-RMS, it also mimics the spread of disease that is observed clinically in RMS originating in the head and neck. Ongoing and future studies include 1) generating highly metastatic human FN-RMS cell lines; 2) using spatial transcriptomics to compare the tumor microenvironment of non-metastatic hindlimb tumors and invasive and/or metastatic lingual tumors; and 3) identifying drivers of FN-RMS dissemination through transcriptomic, genome accessibility, and phospho-proteomic methods. Citation Format: Katie E. Hebron, Kristine Isanogle, Amy James, Simone Difilippiantonio, Marielle E. Yohe. A novel orthotopic xenograft model of spontaneous metastasis for rhabdomyosarcoma using lingual intramuscular injection. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3537.

Abstract 3469: Lymph node colonization promotes distant tumor metastasis through the induction of tumor-specific immune tolerance

Abstract The majority of cancer-associated deaths result from distant organ metastasis, yet the mechanisms that enable this process remain poorly understood. For most solid tumors, colonization of regional or distant lymph nodes (LNs) typically precedes the formation of distant organ metastases, yet it remains unclear whether LN metastasis plays a functional role in disease progression. LNs are major sites of anti-tumor lymphocyte education, including in the context of immunotherapy, yet LN metastasis frequently correlates with further disease progression. Here, we find that LN metastasis represents a critical step in tumor progression through the capacity of such metastases to induce tumor-specific immune tolerance in a manner that promotes further dissemination of tumors to distant organs. Using an in vivo passaging approach of a non-metastatic syngeneic melanoma, we generated 300 unique cell lines exhibiting varying degrees of LN metastatic capacity. We show that the presence of these LN metastases enables distant organ seeding of metastases in a manner that the parental tumor cannot, and this effect is eliminated in mice lacking an adaptive immune response. Furthermore, this promotion of distant seeding by LN metastases is tumor specific. Using flow cytometry and single-cell sequencing to perform comprehensive immune profiling, we identify multiple cellular mediators of tolerance. In particular, we find that LN metastases have the capacity to both resist NK cell cytotoxicity and induce regulatory T cells (Tregs). Furthermore, depletion of NK cells in vivo enables non-metastatic tumors to disseminate to LNs, and ablation of Tregs using FoxP3-DTR mice eliminates the occurrence of lymphatic metastases. Adoptive transfer of Tregs from the LNs of mice bearing LN metastasis to naïve mice facilitates metastasis in a manner that Tregs from mice without LN metastases cannot, and we find that these Tregs are induced in an antigen-specific manner. Whole exome sequencing revealed that neither the metastatic proclivity nor immunosuppression evolve through the acquisition of driver mutations, loss of neoantigens, loss of MHC class I presentation, or decreases in melanoma antigen expression. Rather, by RNA-seq and ATAC-seq, we show that a conserved interferon signaling axis is upregulated in LN metastases and is rendered stable through epigenetic reprogramming of chromatin accessibility resulting from chronic exposure to interferons in vivo. Furthermore, using CRISPR/Cas9, we find that these pathways are required for LN metastatic seeding, and validate their conserved significance in additional mouse models of pancreatic ductal adenocarcinoma and head and neck squamous cell carcinoma and humans with LN metastatic disease. Together, these findings demonstrate a critical role for LN metastasis in promoting tumor-specific immunosuppression. Citation Format: Nathan E. Reticker-Flynn, Weiruo Zhang, Julia A. Belk, Pamela A. Basto, Andrew J. Gentles, John B. Sunwoo, Ansuman T. Satpathy, Sylvia K. Plevritis, Edgar G. Engleman. Lymph node colonization promotes distant tumor metastasis through the induction of tumor-specific immune tolerance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3469.

Abstract 134: Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer

Abstract Backgrounds: Gastric cancer (GC) ranked 5th and 8th on the list of cancer related deaths worldwide and in Taiwan, respectively. Due to its high frequency of lymph node spread, lymph node dissection has become a standard procedure in surgical treatment. A randomized trial showed that patients who underwent D2 lymphadenectomy had a better 5-year survival outcome than ones who had D1 dissection in advanced gastric cancer, implying the D2 lymph node might serve as an outpost before tumor cells spread to distant organs. This clinical observation raises a possibility that the regional lymphatic spread could be under strict selection but not a passive process. Materials and Methods: To understand the evolutionary relationship between primary tumors, perigastric lymph nodes, and second tier of lymph nodes in the extra-perigastric area, we reconstruct their phylogeny using genetic variants in hypermutable DNA regions where the mutation rate is 102~104-fold than unique sequence. We have assembled a cohort of 10 gastric cancer patients, including intestinal-, diffuse- and mixed type GC. For each case, we collected all workable lymph node metastases and intensely sampled primary tumors. On average, we have over fifteen samples per case on the phylogenetic tree. Results: Preliminary data of the first two patients show high heterogeneity within primary tumors as well as between different lesions of lymph nodes or peritoneal metastases in gastric cancer. Interestingly, in stark contrast to all other lymph node metastases which intermingle with primary tumors, a clade consisting of one proximal and one distal lymph node with a bootstrap value above 90% is observed in each phylogeny, and it is worth noting that samples on these clades are from intestinal type tumor. Conclusion: Our results indicate that most tumor cells arrive both regional and distal lymph nodes passively via lymphatic drainage in GC while a selective process also exists which coincides with clinical observation. Whether the existence of tumor cells under a relatively stricter selection process would lead to different clinical outcomes is under investigation. Citation Format: Pei-Chi Cheng, Wei-Ting Hung, Yung-Ming Jeng, I-Rue Lai. Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 134.

Abstract 4369: The effects of primary hepatocellular carcinoma surgical resection on five year survival rates among different races

Abstract Background: Hepatic surgical resection is the treatment of choice for noncirrhotic HCC patients. Previous studies indicate that Asian patients were proportionally more likely to be treated surgically. However, studies on the outcome of this preference are very limited. Methods:We examined data from the Surveillance, Epidemiology and End Results (SEER)-Medicare database to identify patients diagnosed with HCC between 2004 and 2017.The disease specific and relative five year survival rates as well as 95% Cl were calculated. Results:Among the total of 6,716 Asian or Pacific Islander (A/P) patients diagnosed with localized HCC, 45.9% of them received surgical resection. The localized HCC surgical resection rates for White (27,360 total cases) and Black (4,546 total cases) were 35.6% and 33.1% respectively. This pattern remained the same for patients with regional and distant site involved HCC: Highest percentage of A/P patients received surgical resections. For patients with localized HCC, five year cause specific survival rate was statistically higher for A/P patients than White and Black (P&amp;lt;0.05) 24 months after the surgery. These trends continued until the end of the study. For patients with regional HCC, surgical resection played no significant role for the five year cause specific survival rate among the different races. However, for patients with distant involved HCC, five year cause specific survival gap between White and A/P gradually increased after surgery and reached a statistically significant level on month 48 (23.9% with 95% CI 18.6% to 29.6% for White and 9.7% with 95% CI 4.4% to 17.5% for A/P). The pattern remained the same between Black and A/P patients without statistical significance, most likely due to the limited sample size for both.. Our research also indicated that surgical resection may play a similar role for the five year relative survival rate. After localized HCC surgical resection, A/P patients had the highest five year relative survival rate compared to White and Black patients (P&amp;lt;0.05). For the patients with regional HCC, surgical resection played no significant role on five year relative survival rate among different races. However, for the patients diagnosed with distant involved HCC, five year relative survival gap between White and A/P gradually increased after surgery and reached a statistically significant level on month 48 (23.7% with 95% CI 18.3% to 29.4% for White and 10.5% with 95% CI 5.2% to 18.0% for A/P). The pattern remained the same between Black and A/P patients without statistical significance due to the limited sample size in both categories. Conclusion: A/P primary HCC patients were more likely to be treated surgically. However, the benefits of surgical resection for A/P patients can only be appreciated for those with localized HCC. For A/P patients diagnosed with distant site node involved HCC, surgical resection may cause more harm than good. Citation Format: Jingwei Song, Eric Song, Daniel Gharavi. The effects of primary hepatocellular carcinoma surgical resection on five year survival rates among different races. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4369.

Deterministic entanglement distribution on series-parallel quantum networks

The performance of distributing entanglement between two distant nodes in a large-scale quantum network (QN) of partially entangled bipartite pure states is generally benchmarked against the classical entanglement percolation (CEP) scheme. Improvements beyond CEP were only achieved by nonscalable strategies for restricted QN topologies. This paper explores and amplifies a new and more effective mapping of a QN, referred to as concurrence percolation theory (ConPT), that suggests using deterministic rather than probabilistic protocols for scalably improving on CEP across arbitrary QN topology. More precisely, we implement ConPT via a deterministic entanglement transmission (DET) scheme that is fully analogous to resistor network analysis, with the corresponding series and parallel rules represented by deterministic entanglement swapping and concentration protocols, respectively. The main contribution of this paper is to establish a powerful mathematical framework, which is applicable to arbitrary $d$-dimensional information carriers (qudits), that provides different natural optimality metrics in terms of generalized $k$-concurrences (a family of fundamental entanglement measures) for different QN topologies. In particular, we conclude that the introduced DET scheme (a) is optimal over the well-known nested repeater protocol for distilling entanglement from partially entangled qubits and (b) leads to higher success probabilities of obtaining a maximally entangled state than using CEP. The implementation of the DET scheme is experimentally feasible as tested on IBM's quantum computation platform.

Impact of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography on the Therapeutic Decision of Prostate Carcinoma Primary Staging: A Retrospective Analysis at the Brazilian National Public Health System.

Prostate cancer (PCa) is the most common malignant tumor in males and conventional imaging does not provide accurate primary staging. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) presents superior performance and strongly affects therapeutic choice. The aim of this study was to evaluate the impact of PSMA PET, compared with conventional imaging methods, on the therapeutic approach in primary staging scenarios in patients with PCa treated at the Brazilian National Public Health System. Overall, 35 patients diagnosed with PCa were evaluated using PSMA after conventional staging imaging with multiparametric magnetic resonance (MMR) and/or total abdominal computed tomography (CT) scan and bone scintigraphy (BS). The PCa extension identified by PET was compared with conventional imaging; staging changes and the management impact were then determined. PET comparison with conventional imaging, staging, and decision-making changes was analyzed using descriptive statistics. PET revealed local disease (LD) in 15 (42.9%) patients, seminal vesicle invasion (SVI) in 5 (14.3%) patients, pelvic nodal impairment (PNI) in 7 (20%) patients, pelvic and distant nodes in 3 (8.6%) patients, pelvic nodes and bone metastasis in 4 (11.4%) patients, and pelvic and distant nodes and bone metastasis in 1 (2.8%) patient. Staging changes were observed in 60% of patients, with downstaging predominance (76.2%). Volume increase was identified in 11 (31.4%) patients (only 4 related to upstaging, 36.4%). The board changed management decisions for 60% of the patients. The main limitations of this study were the sample size and its retrospective nature. PSMA findings changed the management decisions in more than half of the patients, which made the majority eligible for locoregional treatment and avoided unnecessary procedures in the systemic disease scenario.

Facing adenocarcinoma of distal esophagus and esophagogastric junction: a CROSS versus FLOT propensity score-matched analysis of oncological outcomes in a high-volume institution.

Multimodality treatments are the gold standard for advanced resectable gastroesophageal cancer. Neoadjuvant CROSS and perioperative FLOT regimens are adopted for distal esophageal and esophagogastric junction adenocarcinoma (DE/EGJ AC). At present, none of the approaches is clearly superior in the context of a curative-intent multimodal treatment. We analyzed consecutive patients treated with CROSS or FLOT and surgery for DE/EGJ AC between August 2017 and October 2021. Propensity score matching was performed to balance baseline characteristics of patients. The primary endpoint was disease-free survival. Secondary endpoints included overall survival, 90-day morbidity/mortality rates, pathological complete response, margin-negative resection, and pattern of recurrence. Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. The 2-year DFS rate was 54.2% versus 64.1% in the CROSS and FLOT group, respectively (p = 0.182). Patients in the CROSS group showed a lower number of harvested LN when compared to the FLOT group (29.5 versus 39.0 respectively, p = 0.005). A higher rate of distal nodal recurrence was found in the CROSS group (23.8% versus 4.8%, p = 0.026). Although not significant, the CROSS group showed a trend toward higher rate of isolated distant recurrence (33.3% versus 21.4% respectively, p = 0.328), together with a higher rate of early recurrence (23.8% versus 9.5% respectively, p = 0.062). FLOT and CROSS regimens for DE/EGJ AC offer similar DFS and OS, together with comparable morbidity/mortality rates. CROSS regimen was associated with a higher distant nodal recurrence rate. Results of ongoing randomized clinical trials are awaited.

Retroperitoneal solitary neurofibroma mimicking lymph node metastasis of colon cancer: a case report

BackgroundA neurofibroma is a benign tumor that arises from Schwann cells and neurofibromas occur throughout the skin of neurofibromatosis type 1 (NF-1: Von Recklinghausen’s disease) patients. A retroperitoneal solitary neurofibroma without any clinical signs of NF1 has been rarely reported. Herein, we present a case of a retroperitoneal solitary neurofibroma mimicking lymph node metastasis of colon cancer as well as a literature review.Case presentationAn 80-year-old woman with abdominal pain and nausea was transported and diagnosed with bowel obstruction arising from sigmoid colon cancer A colonic stent was inserted to alleviate the bowel obstruction. A computed tomography scan with contrast revealed a liver tumor in segment 3, and an enlarged lymph node around the abdominal aorta. Whole-body 18F-fluorodeoxyglucose-positron emission tomography–CT (FDG-PET–CT) examine revealed increased FDG uptake in the liver tumor and enlarged lymph node. Liver and distant lymph node metastasis were diagnosed and we made a plan for a two-stage operation of the colon cancer and the metastatic lesions because laparotomy resection was needed for the retroperitoneal lymph node. Laparoscopic sigmoid colectomy was performed first. Pathological examination showed a tubular adenocarcinoma. A laparotomy for the metastatic lesions was performed to ensure complete lymph node dissection secondly. Histopathological findings of the liver tumor showed metastasis of sigmoid colon cancer. However, the tissue regarded as the enlarged lymph node was diagnosed as a neurofibroma. No metastasis and recurrence were observed.ConclusionAlthough most neurofibromas are benign, malignant transformation of a neurofibroma is possible. PET–CT showed our patient had a high accumulated retroperitoneal tumor co-existing with colon cancer and liver metastasis. The treatment strategy of a solitary neurofibroma must be selected carefully considering the site of occurrence and the patient’s background and aggressive resection of a tumor co-existing with another malignant tumor is needed.