Nodal Spread Research Articles

Appendiceal adenocarcinoma-patterns of tumor spread and prognosis

IntroductionAppendiceal adenocarcinoma represents a diagnostic and therapeutic challenge since it is prone to early lymphatic and peritoneal spread. We aimed to analyze the proportion of lymph node metastases in completion right hemicolectomy specimens, risk factors for peritoneal metastases (PM), and prognosis after definitive treatment. MethodsNinety-three patients with appendiceal adenocarcinoma scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in Uppsala 2004–2020 were identified from a prospectively maintained registry. Risk factors for PM were assessed based on the presence (CT + group, n = 55) or absence (CT – group, n = 37) of visible PM at baseline CT scan. Prognostic factors were analyzed based on the actual presence (PM group, n = 66) or absence (no PM group, n = 27) of PM. ResultsThe median age was 60 (26–78). Forty-eight patients were women. Resection of PM at initial surgery indicated an 80 % risk of finding PM at a follow-up exploration. R1 appendectomy and perforated appendix had a similar risk for PM (24 %,26 %) which increased to 38 % if both were present.Regional lymph node metastases occurred in 31 % in the CT + group vs. 14 % in the CT − group (p = 0.005) and was associated with poor survival HR 5.16 (1.49–17.81).The 5-year OS and DFS rates were 54 % and 29 % in the PM group. ConclusionsPatients with certain risk factors have a high likelihood of PM despite a normal CT scan, which justifies selective exploration at a HIPEC center. Regional lymph node spread supports the current practice of completion right hemicolectomy and is a significant prognostic factor.

First-Generation Radiolabeled Cyclic Peptides for Molecular Imaging of Platelet-Derived Growth Factor Receptor α.

Occult nodal spread and metastatic disease require longstanding imaging and biochemical assessments for thyroid cancer, a disease that has a propensity for diffuse, small-volume disease. We have developed a 64Cu-labeled platelet-derived growth factor receptor α (PDGFRA) antibody for immuno-PET of PDGFRA in metastatic papillary thyroid cancer (PTC). The present work describes the discovery of small cyclic PDGFRA-targeting peptides, their binding features, and radiolabeling with positron emitter gallium-68 (68Ga) for in vitro and in vivo characterization in thyroid cancer models. Phage-display technology with two separate libraries and seven different cell lines was used through three rounds of biopanning as well as flow cytometry and comparative analysis with recombinant protein to select specific peptide sequences. Phenotypic binding analysis was completed by using phosphorylation and cell migration assays. In vitro protein binding was analyzed with thermophoresis and flow cytometry using the fluorescent-labeled PDGFRA peptide. Peptide candidates were modified with the NOTA chelator for radiolabeling with 68Ga. In vitro cell uptake was studied in various thyroid cancer cell lines. In vivo studies of 68Ga-labeled peptides included metabolic stability and PET imaging. From the original library (1013 compounds), five different peptide groups were identified based on biopanning experiments with and without the α subunit of PDGFR, leading to ∼50 peptides. Subsequent phenotypic screening revealed two core peptide sequences (CP16 and CP18) that demonstrated significant changes in the level of PDGFRA phosphorylation and cell migration. Alanine scan sublibraries were created from these two lead peptide sequences, and peptides were radiolabeled using 68Ga-GaCl3 at pH 4.5, resulting in RCP > 95% within 34-40 min, including SPE purification. Cyclic peptide CP18.5 showed the strongest effects on cell migration, flow cytometry, and binding by visual interference color assay. 68Ga-labeled PDGFRA-targeting peptides showed elevated cell and tumor uptake in models of thyroid cancer, with 68Ga-NOTA-CP18.5 being the lead candidate. However, metabolic stability in vivo was compromised for 68Ga-NOTA-CP18.5 vs 68Ga-NOTA-CP18 but without impacting tumor uptake or clearance profiles. First-generation radiolabeled cyclic peptides have been developed as novel radiotracers, particularly 68Ga-NOTA-CP18.5, for the molecular imaging of PDGFRA in thyroid cancer.

467. DISTRIBUTION OF LYMPH NODE INVOLVEMENT IN PATIENTS WITH GASTRO-ESOPHAGEAL JUNCTION ADENOCARCINOMA

Abstract Background Curative cancer surgery relies on understanding the lymphatic spread of the tumour to guide lymphadenectomy. The lymphatic involvement in patients with esophageal squamous cell carcinoma (SCC) has been evaluated extensively in large cohort studies from the East where SCC predominates, but the pattern of lymph node spread in gastro-esophageal junction (GEJ) adenocarcinoma is less clear. The primary aim of this study was to compare differences in the pattern of lymph node involvement according to the Siewert classification. Methods Consecutive patients who underwent curative resection for GEJ adenocarcinoma between February 2010 and April 2023 were analysed from a prospectively maintained database. Patient demographic data, neo-adjuvant treatment, operation type and histopathological report data were collected and analysed according to the pathological Siewert classification of GEJ cancer. Results 807 patients who underwent curative surgery for GEJ adenocarcinoma were analysed. The median lymph node yield was 26 (5-81). Comparing positive para-esophageal node yields, Type I and II tumours were similar but both significantly higher than Type III. For positive para-gastric nodes, Type 2 and 3 tumours were similar but both significantly higher than type 1. The significance of these comparisons is presented in table 1. There were no differences comparing other specific nodal groups. Evaluating the effect of node involvement on overall survival positive node status and positive hepatic artery nodes were found to be independent factors adversely affecting survival. Conclusion Siewert type I tumours have greater proximal lymph node involvement compared to type III tumours with higher proportions of positive para-esophageal nodes. Type III tumours on the other hand have higher proportions of para-gastric nodes. Type II tumours have similar para-esophageal node involvement to type 1 tumours and similar para-gastric involvement to type III tumours. Involvement of more specific nodal groups does not seem to vary between the sub types.

637. UPFRONT SURGERY IN ESOPHAGEAL CANCER: ACCURACY OF PREOPERATIVE CLINICAL STAGING

Abstract Background Treatment of locally limited esophageal cancer is still a frequently discussed topic. Especially, the inaccuracy of clinical staging in lymph node-negative T2-carcinomas has to be considered further in the treatment pathway. Aim of this study was to evaluate the accuracy of clinical staging in patients treated with esophagectomy without neoadjuvant treatment. Methods We conducted a retrospective multicenter analysis at the departments of surgery from two university clinics. All patients between January 2016 and December 2023, who underwent an esophagectomy because of an esophageal adenocarcinoma or squamous cell carcinoma without neoadjuvant treatment were included. Advanced tumor stage, T staging greater than T2, was defined as exclusion criteria. Results Fifty-three patients after upfront esophagectomy were included in the analysis. In 40 (75%) patients a gastroesophageal junction adenocarcinoma was diagnosed, and 13 (25%) patients were treated because of a squamous cell carcinoma of the esophagus. Clinical T staging was T1 or T2 and all lymph node stages were included. The endosonographic preoperative staging of invasion depth was accurate in 32 (60%) patients in comparison to the histopathological staging. In 7 (13%) cases the T-values were upstaged one level and in 5 (9%) cases one level downstaged after resection. The endosonographic preoperative staging of nodal spread was accurate in 32 (60%) patients. Furthermore, in 7 (13%) cases node status was upstaged and in 5 (9%) patients downstaged. Nine (17%) patients did not undergo a sufficient endosonographic staging, mainly due to prior endoscopic submucosal dissection or stenosis. In these patients, clinical lymph node staging was accurate in 4 patients. Conclusion Preoperative staging using endoscopic ultrasound and computed tomography is not accurate enough in a high number of patients, therefore we are seeking to identify other predictive factors underlying advanced stage esophageal cancer.

Influence Maximization Based on Adaptive Graph Convolution Neural Network in Social Networks

The influence maximization problem is a hot issue in the research on social networks due to its wide application. The problem aims to find a small subset of influential nodes to maximize the influence spread. To tackle the challenge of striking a balance between efficiency and effectiveness in traditional influence maximization algorithms, deep learning-based influence maximization algorithms have been introduced and have achieved advancement. However, these algorithms still encounter two key problems: (1) Traditional deep learning models are not well-equipped to capture the latent topological information of networks with varying sizes and structures. (2) Many deep learning-based methods use the influence spread of individual nodes as labels to train a model, which can result in an overlap of influence among the seed nodes selected by the model. In this paper, we reframe the influence maximization problem as a regression task and introduce an innovative approach to influence maximization. The method adopts an adaptive graph convolution neural network which can explore the latent topology information of the network and can greatly improve the performance of the algorithm. In our approach, firstly, we integrate several network-level attributes and some centrality metrics into a vector as the presentation vector of nodes in the social network. Next, we propose a new label generation method to measure the influence of nodes by neighborhood discount strategy, which takes full account of the influence overlapping problem. Subsequently, labels and presentation vectors are fed into an adaptive graph convolution neural network model. Finally, we use the well-trained model to predict the importance of nodes and select top-K nodes as a seed set. Abundant experiments conducted on various real-world datasets have confirmed that the performance of our proposed algorithm surpasses that of several current state-of-the-art algorithms.

Outcomes of Differentiated Thyroid Cancer in Children and Adolescents at King Abdulaziz Medical City, Jeddah.

Objective Differentiated thyroid cancer (DTC) is rare in the pediatric population, with most data from the Western world. We aimed to describe the clinical presentation, treatment intervention, histopathological characteristics, complications, follow-up, and response to treatment in 17 patients with DTC at or below the age of 20 years. Interventions This was a retrospective cohort study at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included patients aged younger than 20 years with DTC. Total or near-total thyroidectomy was performed in 82% of the patients, central and/or lateral neck dissection in 35% of cases, and radioactive iodine (RAI) ablation in 76% of cases. Results The study included 17 patients (14 females), with a median age of 16 years at the time of diagnosis. Thyroid nodules were the main complaint in 88% of the patients. Thyroid ultrasonography was the main method for the initial evaluation. Papillary cancer was the most common type of tumor, and lymph node spread was found in 82% of the patients. Moreover, 40% of the patients exhibited excellent responses to therapy, with 35% showing indeterminate results. Only 23.5% of the patients developed hypocalcemia postoperatively. Conclusions Classical papillary thyroid carcinoma was the predominant histopathological type, and most patientsshowed excellent responses to therapy, followed by indeterminate in most of the cases. The most common presentation was a neck nodule, signifying the role of thorough physical neck examinations. Finally, recurrence occurred in a minority of patients. However, none of these patients died.

Functional variants of the pentraxin 3 gene are associated with the metastasis and progression of prostate cancer.

Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern-recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer-associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single-nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity-matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically-confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age-specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa.

The Incidence of Breast Cancer Lymph Node Involvement in Trinidad and Tobago.

Objective This study aims to investigate breast cancer lymph node involvement in a West Indian population whilecorrelating it with various histological parameters and evaluating the role of the sentinel lymph node biopsy. Method This is a retrospective study where histology reports for all breast cancer-related biopsies from 2018 to 2021, totaling 813 samples, were obtained. Histological parameters from these reports were extracted into a spreadsheet andanalyzed usingStatistical Product and Service Solutions (SPSS, version 28.0; IBM SPSS Statistics for Windows, Armonk, NY) software for TNM staging and axillary and sentinel lymph node dissections, among other fields found in histology reports. Results In 44.8% of cases, patients present at the T2 stage with associated lymph node spread. Each T stage had more lymph nodes involved than uninvolved for tumors sized T2 and higher. Inversely, for tumors staged under T2, there were generally more uninvolved lymph nodes than involved ones. Larger tumors were found to have advanced N staging, especially in the T3 category, where a significantly higher proportion of cases were found to have N2 and N3 staging compared to the other T stages. This trend is also seen in M staging, where larger tumors metastasize more than smaller tumors (40% for T4a, 0% for T1). Despite significant lymph node involvement being observed, sentinel lymph node biopsies were usually negative. Conclusion More patients in this population present with lymph node involvement than without. Larger breast cancer tumors are associated with greater lymph node involvement, particularly at T2 and higher stages. Sentinel lymph node biopsies can be omitted in smaller breast cancer tumors up to 2 cm in size, and the local recurrence rate is low despite a false-negative rate of around 10% in upfront sentinel lymph node biopsy.

Anatomical Patterns of Nodal Spread in Unilateral Papillary and Medullary Thyroid Cancer.

Background: Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Methods: This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Results: Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6-78.1% of patients with PTC (both node positive in 27.0-54.7% and both node negative in 23.4-49.6%) and 77.3-80.0% of patients with MTC (both node positive in 26.6-33.2% and both node negative in 44.1-53.4%). Only one ipsilateral neck compartment was node positive in 21.9-23.4% of patients with PTC and 20.0-22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8-16.9% with PTC and 8.6-8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5-13.1% with PTC and 11.3-14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5-2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2-25.2% vs. 12.9-17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. Conclusions: These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments.

Characterisations and Scan Findings of Non-Small Cell Lung Cancer Seen on Staging FDG PET-CT: Contemporary Review and Institutional Experience

Objective: Fluorodeoxyglucose (FDG) PET-CT scan is extensively being applied in oncology including lung cancer staging and treatment response assessment by depicting glucose consumption of malignant cells. Non- small cell lung cancer (NSCLC) cases such as adenocarcinoma and squamous cell carcinoma (SCC) are more prevalent. We aimed to determine the FDG uptake avidity based on semiquantitative maximum Standardise Uptake Value (SUVmax) observed on staging PET-CT of newly diagnosed NSCLC and associated contributing factors. Methods: Retrospective review of 125 cases of biopsy proven lung cancer referred for FDG PET-CT in our institution over the past 2 years. Staging PET-CT scans (n=54) were included for analysis. Clinical parameters and PET-CT findings (SUVmax of primary lesion, presence of nodal and metastatic disease) were investigated. SUVmax of primary lesion for SCC and adenocarcinoma was compared. Association between SUVmax of primary lesion and extrapulmonary FDG- avid lesions presence was also determined. Results: Males were predominant (60%). Average age was 62.5 years. Majority were adenocarcinoma (65%) followed by SCC (22%) and others (13%). Mean tumour size was 5.1 cm. Lung SCC demonstrated intensely increased FDG uptake that was significantly higher compared to adenocarcinoma (average SUVmax 24.4 vs SUVmax 15.6, p<0.05). FDG-avid ipsilateral hilar nodal involvement seen in 63%, mediastinal nodes in 70% while distant metastatic disease in 33%. Patients having primary lesion with SUVmax 20.0 and above were significantly associated with larger tumour size and FDG-avid ipsilateral hilar nodal uptake (p<0.05). Conclusion: Lung SCC was intensely FDG-avid and had higher SUVmax compared to adenocarcinoma. Primary lesions with SUVmax 20.0 and above were associated with larger tumour size and presence of hypermetabolic ipsilateral hilar nodal spread. Information obtained from this review will provide valuable insight into PET-CT scan characteristics of newly diagnosed NSCLC cases in our institution that may influence not only scan reporting formulation but also patient management.International Journal of Human and Health Sciences Supplementary Issue 01: 2024 Page: S46

Identification of key nodes in complex networks by using a joint technique of nonnegative matrix factorization and regularization

Identifying key nodes in complex networks is essential to deeply understand and fully utilize the properties and functions of complex systems. Currently, existing traditional methods perform critical nodes identification by manually selecting important attribute features of nodes, but there are limitations in this approach. Manual selection of attribute features may overlook non-obvious features related to nodes criticality and correlations between attribute features. To compensate for the shortcomings of traditional methods, a Joint Technique for identifying critical nodes, called JTNMFR, is presented based on Nonnegative Matrix Factorization and Regularization. Factorization of weighted adjacency matrix is performed to obtain potential attribute features of nodes, and communicability network matrix and similarity matrix are introduced as regularization terms to control sparsity of the decomposition results. Ultimately, the importance of nodes is assessed by constructing an objective function that integrates these two aspects and utilizing alternative iteration to obtain the attribute matrix. To validate the accuracy and reliability of JTNMFR, we compare it with nine other identification approaches on eight real networks. Experimental results show that JTNMFR not only significantly outperforms the other algorithms in terms of accuracy of node importance, monotonicity, and node spreading ability but also provides a more accurate means of assessing node importance.

Identifying influential spreaders in complex network based on the node’s weight and spreading probability

Identifying influential spreaders is a crucial aspect of network science with various applications, including rumor control, viral marketing and epidemic spread limitation. Despite the availability of various methods for identifying these spreaders in complex networks, there remains a fundamental question regarding their accurate and discriminative identification. To address the issues and account for each node’s propagation ability, we propose an algorithm to identify influential spreaders based on the node’s weight and spreading probability (NWSP) for identifying influential spreaders. The effectiveness of the proposed method is evaluated using the Susceptible–Infected–Recovered (SIR) model, Kendall’s Tau ([Formula: see text]) and monotonicity. The proposed method is compared with several well-known metrics, including degree centrality, K-shell decomposition, betweenness centrality, closeness centrality, eigenvector centrality and the centrality method based on node spreading probability (SPC), in ten real networks. Experimental results demonstrate the superiority ability of the proposed algorithm to accurately and discriminatively identify influential spreaders.

TNM stage in the Nordic Cancer Registries 2004-2016: Registration and availability.

Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies. TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries. Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries. Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Incidence of Lymphovascular Emboli, Perineural Invasion and Lymph Node Spread with Relation to Tumour Grading in Oral Cancer Specimen in Konkan Region

Incidence of Lymphovascular Emboli, Perineural Invasion and Lymph Node Spread with Relation to Tumour Grading in Oral Cancer Specimen in Konkan Region

Tumor-associated macrophages and tumor-infiltrating lymphocytes in canine cutaneous and subcutaneous mast cell tumors.

Cutaneous and subcutaneous mast cell tumors (MCTs) are common canine neoplasms characterized by variable biological behavior. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) can be effective prognostic markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine MCTs and their relationship with histological location (cutaneous, subcutaneous) and histologic nodal metastatic status (HN0-3). Thirty-eight MCTs (26 cutaneous, 12 subcutaneous) from 33 dogs with known sentinel lymph node (SLN) metastatic status were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). Semiquantitative scoring of interstitial and perivascular CD3+, CD20+, and Foxp3+ cells and morphological evaluation of Iba1+ cells were performed. For each marker, the percent immunopositive area was evaluated by image analysis. All MCTs were diffusely infiltrated by Iba1+ cells and variably infiltrated by CD20+, CD3+, and rare Foxp3+ cells. Stellate/spindle Iba1+ cells were associated with HN2 and HN3 SLNs. Perivascular Foxp3+ cells, CD3+ cells, and percent CD3+ areas were increased in subcutaneous MCTs. Interstitial CD3+ cells were increased in cutaneous MCTs with HN0 SLNs. No differences in CD20+ cells were identified between cutaneous and subcutaneous MCTs and among SLN classes. MCTs were markedly infiltrated by TAMs and variably infiltrated by TILs. Stellate/spindle morphology of TAMs associated with HN2 and HN3 SLNs is suggestive of a pro-tumoral (M2) phenotype. Cutaneous and subcutaneous MCTs have different tumor-immune microenvironments, and T-cell infiltration might contribute to prevention of nodal metastatic spread of cutaneous MCTs.

Predicting nodal influence via local iterative metrics

Nodal spreading influence is the capability of a node to activate the rest of the network when it is the seed of spreading. Combining nodal properties (centrality metrics) derived from local and global topological information respectively has been shown to better predict nodal influence than using a single metric. In this work, we investigate to what extent local and global topological information around a node contributes to the prediction of nodal influence and whether relatively local information is sufficient for the prediction. We show that by leveraging the iterative process used to derive a classical nodal centrality such as eigenvector centrality, we can define an iterative metric set that progressively incorporates more global information around the node. We propose to predict nodal influence using an iterative metric set that consists of an iterative metric from order 1 to K produced in an iterative process, encoding gradually more global information as K increases. Three iterative metrics are considered, which converge to three classical node centrality metrics, respectively. In various real-world networks and synthetic networks with community structures, we find that the prediction quality of each iterative based model converges to its optimal when the metric of relatively low orders (K∼4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K\\sim 4$$\\end{document}) are included and increases only marginally when further increasing K. This fast convergence of prediction quality with K is further explained by analyzing the correlation between the iterative metric and nodal influence, the convergence rate of each iterative process and network properties. The prediction quality of the best performing iterative metric set with K=4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K=4$$\\end{document} is comparable with the benchmark method that combines seven centrality metrics: their prediction quality ratio is within the range [91%,106%]\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$[91\\%,106\\%]$$\\end{document} across all three quality measures and networks. In two spatially embedded networks with an extremely large diameter, however, iterative metric of higher orders, thus a large K, is needed to achieve comparable prediction quality with the benchmark.

Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance.

To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LN). Patients with NPC harboring at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in nonrestricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs. In all, 5,836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm, and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm, and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively. In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.

The boundary of posterior to level V region and the theoretical feasibility of irradiation dose reduction of level Va in nasopharyngeal carcinoma

The lymph node involvement in the posterior to level V (PLV) region is mainly observed in nasopharyngeal carcinoma (NPC). Recently, we have reported the distribution of metastatic lymph nodes in the PLV region and there are correlations between the neck node levels (NNL) of NPC, but what is the boundary of the PLV region and how to delineate it remains unclear, and we further to elaborate whether the bilateral level Va should be covered as intermediate-risk nodal regions (CTVn2, about 60 Gy equivalent) for all T and N categories based on these correlations. A total of 1021 consecutive NPC patients with N1-3 stage from January 2012 to December 2020 were reviewed. The lymph node metastasis level of each patient was evaluated according to the updated guidelines proposed in 2013. According to the distribution pattern of lymph node metastasis and the anatomical structure in the PLV region, the boundaries of PLV region was delineated, and whether it is appropriate to cover the bilateral level Va as CTVn2 for all the NPC patients was further discussed. The correlations of level Va with other NNL were studied using logistic regression model. The cranial boundary of PLV region is the caudal border of cricoid cartilage, the caudal boundary is the plane serratus anterior muscle begins to appear, the anterior boundary is the anterior border of trapezius, and the posterior boundary is the convergence of levator scapulae and trapezius. Laterally, the PLV region is limited by the medial edge of trapezius and medially by the lateral surface of levator scapulae. The nodal spread in level Va is based on the lymph node metastasis of level IIb in NPC. The PLV region is a missing NNL of head and neck tumors, especially in NPC. The proposed boundaries of the PLV region can provide a preliminary proposal for the further revision of NNL in head and neck tumors. It is theoretically feasible to reduce the prophylactic irradiation dose of the bilateral level Va in patients with N0 stage or with isolated metastases in level VIIa.

Gradual and synergistic correlation of tumor thickness and histological grade in penile invasive carcinomas

Histological grade and depth of invasion are among the best outcome pathological predictors in penile cancer. The TNM system is based on a combination of both for some stages. It is assumed that high-grade and deep tumors carry the worst prognosis, and the opposite occurs with superficial and low-grade neoplasms. However, there is no systematic evaluation of the phenomenon. We studied 147 patients from the Hospital de Oncologia - Instituto Mexicano del Seguro Social (period 2000 to 2013). They were treated by total or partial penectomies. Lymph node involvement was evaluated by bilateral inguinal node dissection (126 cases) or ultrasonography (21 cases). Tumor thickness was measured in mm from tumor surface to deepest invasion point, using a cut-point for superficial (≤10 mm) vs deep (>10 mm) tumors. Histological grade was from 1 to 3 according to WHO and AFIP criteria and considering G1 and G2 as low-grade and G3 as high-grade. Average age was 62 (26–98) years old. Tumor thickness mean was 15 mm (2–30 mm). G1, G2 and G3 tumors corresponded to 19 (13 %), 48 (33 %), and 80 (54 %) cases, respectively. Follow-up ranged from 10 to 82 months (median: 57 months). Fifty-three (36 %) patients died of disease. There was an overall correlation of tumor thickness and grade in most of the cases. Low-grade tumors were encountered in 92 % (12/13 cases) of superficial tumors. Deep tumors showed high-grade in 75 % of cases (73/97 cases). Superficial tumors with low histological grade had negative inguinal nodes and no mortality whereas deep tumors showing high histological grade were associated with high metastatic risk to lymph nodes (62/73 cases) and mortality (52/73 cases). Out of 24 deep tumors with low histological grade, seven had nodal spread (29 %) but only one died of disease. No outcome difference was found in HPV associated vs HPV independent tumors. Tumor thickness and grade are important synergistic and predictive pathological factors in relation to prognosis.

MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers—Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.