Distant Nodes Research Articles

Synchronous cancers of the stomach and esophagus in a patient with autoimmune gastritis and pernicious anemia: a case report and review of the literature.

Type-A gastritis/autoimmune gastritis (AIG) has gained renewed attention due to declining Helicobacter pylori infection rates and increasing eradication. AIG is associated with pernicious anemia (PA) and is prone to complicate various tumors, such as gastric cancer and neuroendocrine tumors. This report describes a case of AIG with PA in which gastric and esophageal cancers arose simultaneously. An 86-year-old woman had been diagnosed with PA and AIG 9 years earlier. As routine blood tests revealed high levels of carcinoembryonic antigen, she underwent esophagogastroduodenoscopy, which revealed a type 0-IIa lesion in the middle part of the stomach and a type 0-IIa + IIb lesion in the lower esophagus. Endoscopic submucosal dissection was performed on both lesions, since neither distant nor lymph node metastases were identified. Histological examination showed gastric tubular adenocarcinoma and esophageal squamous cell carcinoma. Immunohistology revealed that cells from neither cancer expressed gastrin, gastrin receptor, or p53. Whole-exome sequencing showed 8 gene mutations in the esophageal cancer and 6 mutations in 5 genes in the gastric cancer. The reason for the lack of p53 immunostaining was that TP53 was mutated in these cancers, although TP53 mutations differed. Thus, TP53 mutations may not be detected by immunostaining alone. When treating patients with AIG/PA, clinicians must be aware of the possibility of esophageal cancer coexisting with gastric cancer.

Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma

BackgroundThe beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial.MethodsWe conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis.ResultsOf 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09–4.90; P = 0.029).ConclusionsPD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

e21522 Background: Despite the drastic improvement in survival of patients with metastatic melanoma from immune checkpoint inhibitors (ICIs), almost half of patients still die from their disease. Factors surrounding death including mechanisms of death, sites of disease, and settings of death remain poorly described. A better understanding of these factors is paramount to optimize management for these patients. Methods: A retrospective observational cohort study was performed for patients age &gt; 18 who died after treatment for advanced melanoma with anti-PD1 therapy or ipilimumab + nivolumab (Ipi/Nivo) at Yale Cancer Center (YCC) between 1/2009 and 6/2023. Primary outcome was cause of death. Statistical analyses were performed with Stata SE, version 15.0 (StataCorp, College Station, TX). This study was approved by the Yale Institutional Review Board (Protocol #2000034631). Results: Overall, 287 patients with melanoma who received ICIs were documented to be deceased; 183 met inclusion criteria. Median time from metastatic diagnosis to death was 16.1 mos (range 0.3 to 135.1 mos). Median age at death was 70 (range 22-101), 62.8% were male, and 90.2% were white. Most patients (52.5%) received Ipi/Nivo first line, and 79.8% of patients received both anti-PD1 and anti-CTLA4 treatment at some point. The median number of metastatic sites at death was 4 (range 0-13). The majority (90.1%) of patients with measurable disease had multi-system involvement of melanoma. Eleven patients had no evidence of disease at death and died due to non-melanoma causes. The most common sites of metastatic disease at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). In total, 80.3% (147/183) experienced hospitalization within 3 months prior to death or hospice enrollment. Most died in the hospital (31.7%) or while enrolled in hospice (31.2% inpatient vs. 29.4% home). Overall, 10.9% of patients had survival &gt; 5 years after metastatic diagnosis; 76.2% of long-term survivors died due to melanoma. Of 174 patients with evaluable causes of death, 87.9% of deaths were due to melanoma (Table 1). Patients with pleural metastases were more likely to die of respiratory failure (p = 0.036, OR 2.41 95% CI 1.06-5.50). Conclusions: The majority of deaths were a consequence of metastatic melanoma, with the most common causes including FTT, respiratory failure, and infection. [Table: see text]

Metastatic testicular cancer (TC) presentations and outcomes: A contemporary analysis based on the National Cancer Database (NCDB).

e17016 Background: While most cases of testicular cancers are cured, patients with metastatic or refractory disease continue to have a poor prognosis in recent years (Shah et al; Urology 2023). We sought to determine sites of metastases and survival based on the National Cancer Database (NCDB). Methods: We extracted patient-level data from the NCDB during 2004 to 2020, and identified incidence, demographics, regional differences, treatment, metastatic sites and outcomes in men who had testicular cancer diagnoses (non-seminoma, NS; seminoma, S) with differences in metastatic presentation and outcomes. Results: There were 89550 pts in all, 51623 S pts and 37927 NS pts. Median age for S pts was 37 years and NS was 29 years. 81571 pts were White, 2860 pts were Black. 5396 S pts identified as Hispanic (H) and 5609 NS pts H with other races/unknown for the rest. More S patients were treated at comprehensive community cancer programs (17%) compared to NS pts (6.1%). The majority of patients had a Charlson-Deyo Score of 0 (92.7% of S pts and 93.7% of NS pts), had private insurance (74.1% S pts, 69.1% NS pts). Most were diagnosed with Stage I (29.6%) and Stage II and III (16.3%) though it was unknown/missing for 54%. Overall survival (OS) was better for S compared to NS in all pts (p&lt;0.0001), and in stages II &amp; III (p&lt;0.001). OS was similar for S compared to NS for brain metastasis presentation (p=0.6776), lung (p=0.8967), liver (p=0.1688), but better for S compared to NS for bone metastases (p=0.0002) and distant lymph nodes (p=0.0.0392). Conclusions: Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma in bone and distant lymph node metastases though not for brain, lung and liver metastases, highlighting the need for better therapies for the poorest prognostic groups of TC patients.

Systematic therapy for metastatic solid pseudopapillary neoplasm of the pancreas: A single-center experience.

e16341 Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor with low-grade malignancy. However, a small proportion of cases still exhibit more aggressive behavior and emerge as distant metastases. Limited data exist on systemic therapy for these entities. Methods: A retrospective analysis was performed on patients diagnosed with SPN of the pancreas who underwent medical treatment in our hospital between January 2020 and December 2023. The clinicopathological characteristics and therapeutic regimens of the patients were collected. The primary outcomes were disease control rate (DCR) and progression free survival (PFS). SPSS software V27.0 was used for data analysis. Results: Five patients were identified and 60.0% of patients were female . The median age was 34 years (range 16-53). All patients first underwent surgical resection. Four individuals had metachronous distant metastasis and one had synchronous distant metastasis. The most common metastatic site was peritoneum (3/5) and liver (3/5), followed by the distant lymph node (2/5). Progesterone receptor positive expression was found in four cases. Four patients received targeted therapy as first-line treatment (3 receiving anlotinib 12mg once daily on days 1-14 every 3 weeks and 1 receiving everolimus 10mg per day). All patients receiving targeted therapy had stable disease, with a DCR of 100%. The median PFS in the targeted therapy group was 8.1 months (95% CI, 6.7-9.5). Only one patient underwent first-line chemotherapy (gemcitabine plus S-1) and experienced disease progression at the initial efficacy evaluation. Data for second-line treatment was available for three patients. One patient got progressive disease (PD) after etoposide administration. Two individuals received everolimus 10mg daily, one of whom showed PD and the other achieved a partial response (PR). All treatment-related adverse events (AEs) were manageable. Conclusions: Metastatic SPN of the pancreas may be not chemosensitive. Targeted therapy, such as anlotinib and everolimus, appears to be a potential therapeutic option.

Outcome of prostate cancer with CNS metastasis: An analysis of SEER database (2010-2020).

e17037 Background: Brain metastasis from prostate cancer is rare, with an estimated incidence of &lt;1%, and its characteristics and outcomes are poorly understood. We report a contemporary analysis of outcomes in patients with CNS metastasis from prostate cancer in association with clinicopathological variables by utilizing the Survival, Epidemiology, and End Result (SEER) database with data from 2010 to 2020. Methods: From the SEER database, we identified histologically confirmed primary prostate cancers with any distant metastasis. Data for survival as well as multiple clinicopathological variables including age, race, prostate-specific antigen (PSA) level, Gleason score, prior radiotherapy, histology, and specific metastatic sites were extracted. Statistical analysis included chi-square. ANOVA, and Kaplan-Meier analysis for overall survival (OS) and disease-specific survival. Results: SEER database (2010-2020) identified 27,501 patients with metastatic prostate cancer, of which 27,118 (98.6%) were adenocarcinoma and 383 (1.4%) were prostate cancer with neuroendocrine features. Brain metastasis was seen in 282 (1.04%) and 15 (5.32%) patients in these histologic groups, respectively. Brain metastases were associated with worse prognosis with median OS of 14 months compared to bone-dominant and non-regional lymph node only diseases that showed median OS of 31 months and not reached, respectively (P &lt; 0.01). Within the population with brain metastases, outcome comparison based on age (&lt;65 vs. ≥65 years), ethnicity (Caucasian vs. African American vs. Hispanic), PSA (&lt;98 vs. ≥98 ng/ml), and Gleason score (&lt;9 vs. ≥9) showed no statistically significant difference (table). Presence of metastasis to other solid organs showed numerically worse outcome without statistical significance (OS: 26 months vs. 13 months, p=0.09). Significant OS difference was observed between the adenocarcinoma and neuroendocrine tumor within the brain metastasis subgroup (OS: 14 months vs. 6 months, p=0.03). Conclusions: CNS metastasis with prostate cancer carries worse prognosis in comparison to metastases to bone or distant lymph-nodes. Neuroendocrine tumor has higher risk of CNS metastasis although most of such cases are from adenocarcinoma due to its higher prevalence. OS analysis confirms worse outcome with neuroendocrine features compared to adenocarcinoma in CNS metastatic settings. [Table: see text]

Exploration and prognostic analysis of two types of high-risk ovarian cancers: clear cell vs. serous carcinoma: a population-based study

BackgroundOvarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers.MethodsPatients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3).ResultsIn the Cox analysis for advanced OCCC, age (45–65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes.ConclusionAdvanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.

Axitinib in combination with anti–PD-1 ab (pucotenlimab) plus intra-hepatic injection of oncolytic virus (OH2), in patients with mucosal melanoma and liver metastasis: An open-label phase I trial.

e21524 Background: The combination of anti-PD-1 plus axitinib as systemic therapy had promising antitumor activity in mucosal melanoma, but with limit effect in mucosal melanoma with liver metastasis, which might due to immunosuppression in liver metastasis. Oncolytic virus can heighten the immune response and turn over the immunosuppressive state, which has shown its efficacy in liver metastaic as Intra-hepatic injection. So we initiated this phase I study to evaluate axitinib combination with anti–PD-1 ab plus oncolytic virus in liver metastasis mucosal melanoma. Methods: Eligible pts included those over 18 years old, mucosal melanoma with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis. Pts received intravenous pucotenlimab Q3W combined plus axitinib 5 mg orally twice a day, combined with ultrasound guided intratumoral injection of OH2 Q2W (107CCID50/mL, 8ml per injection). Liver biopsy would be performed at first tumor evaluation (8-12weeks). The primary endpoint was ORR; secondary endpoints included toxicity, disease control rate (DCR), PFS and OS. Results: From Dec 2021 to Jan 2024, 20 pts were eligible and enrolled. Baseline characteristics: median age 56 yrs; 70% got previous treatment, (35% PD-1 resistant). 90% got extra-hepatic metastasis: regional or distant lymph node 45%, lung 40%,; LDH&gt;ULN 50%; median size of target lesions: 61.5mm(12-155mm); median number of liver metastasis: 3(1-18) with median liver lesions 42.5mm(13-230mm). Till the last flow up, 15 pts were evaluable with a median follow-up of 9.39 months. The global ORR was 26.7% (4/15) with 42.9% lesionshrink, injection lesions decrease (43.8%) and non-injection lesion 23.1%. The DCR was 46.7% (7/15). There are still 8 pts on treatment at last follow up. The median PFS was 4.5m, and no pts who had response showed progression till last follow up, the mean DOR was 11.0m. Median OS is not reached. Biopsies of 13 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of tumor regression and TIL infiltration. Among them, 3 pts (2 PD and 1 PR) had no melanoma cells residual by immunohistochemistry with impressive TIL infiltration. The biopsy showed better pathological response than radiological response which might explain some pts still got survival benefit on treatment after radiological PD. Most adverse events (AE) were grade 1-2 and manageable. Grade 3-4 treatment-related AE showed 30% pts, with diarrhea and oral ulceration as the most common. No treatment-related deaths occurred. Conclusions: Systemic anti-PD-1 plus axitinib combined intralesional injection of Oncolytic virus has shown preliminary efficacy in mucosal melanoma pts with liver metastases with manageable toxicity. Clinical trial information: NCT04206358 , NCT05070221 .

412P Survival outcome and safety of different treatment models in patients with oligometastatic esophageal cancer with only distant lymph node metastasis

412P Survival outcome and safety of different treatment models in patients with oligometastatic esophageal cancer with only distant lymph node metastasis

Docetaxel plus cis-platinum chemotherapy for the posterior line treatment of metastatic castrate-resistant prostate cancer with elevated neuron specific enolase.

e17042 Background: This Study is to figure out the efficacy of docetaxel plus cis-platinum (DC) chemotherapy as the posterior line treatment for metastatic castrate-resistant prostate cancer (mCRPC) with elevated neuron specific enolase (NSE). Methods: We performed a retrospective study of men suffered mCRPC with elevated NSE from December 2019 to August 2022. All men were treated with DC after resistance to previous therapy. Biochemical progression-free survival (BPFS) were depicted using Kaplan-Meier curves. Results: 10 mCRPC patients aged 65.8 ± 7.0 (Median: 66.5, Range: 52-77) received DC for 1 to 10 cycles (Median: 7). Of the 10 patients, 2, 1 and 7 patients underwent DC as the 2nd, 3rd and 4th line therapy, respectively. 3 patients received previous chemotherapy and 9 patients underwent new endocrine therapy. All patients suffered bone metastases, 6 patients suffered distal lymph node metastases and 3 patients suffered visceral metastases. 6.1 ± 2.8 cycles (Median: 7, Range: 1-10) of DC were finished. Median follow-up time was 6.5 (Range: 2-11) months. After DC, Prostate specific antigen (PSA) response rate (&gt;50%) was 90% and NSE response rate (&gt;50%) was 60%. Median BPFS was 10 (Range: 4-18) months. Pain score declined from 6.6 ± 3.1 to 3.9 ± 2.4 evidently (P &lt; 0.05) and Karnofsky (KPS) score increased from 80 ± 14.9 to 91 ± 16.0 significantly (P &lt; 0.05). Of the 6 patients assessed by radiological examinations, 5 patients experienced partial response and 1patient achieved stable disease. Conclusions: Our pilot study showed docetaxel plus cis-platinum chemotherapy was effective for the mCRPC patients with elevated NSE resistant to multi-line therapies, indicating the potential value of DC for mCRPC with neuroendocrine differentiation.

Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes.

As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.

METTL5 promotes gastric cancer progression via sphingomyelin metabolism.

The treatment of gastric cancer (GC) has caused an enormous social burden worldwide. Accumulating studies have reported that N6-methyladenosine (m6A) is closely related to tumor progression. METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells. However, its aberrant regulation in GC has not been fully elucidated. To excavate the role of METTL5 in the development of GC. METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples. The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays, colony formation assays, scratch healing assays, transwell assays and flow cytometry. The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model. The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification. Next, liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism, which was confirmed by Enzyme-linked immunosorbent assay and rescue tests. In addition, we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments. Our research revealed substantial upregulation of METTL5, which suggested a poor prognosis of GC patients. Increased METTL5 expression indicated distant lymph node metastasis, advanced cancer stage and pathological grade. An increased level of METTL5 correlated with a high degree of m6A methylation. METTL5 markedly promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 also promotes the growth of GC in animal models. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism, which implies that METTL5 may impact the development of GC via sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance. METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

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.

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&amp;lt; 0.001) and OS (HR 0.48, 95% CI 0.40-0.58; P&amp;lt; 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 &amp;gt; 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&amp;lt; 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.

Study on the evaluative value of abdominal multi-slice spiral CT examination for distant metastasis and regional lymph node metastasis in colorectal cancer.

Study on the evaluative value of abdominal multi-slice spiral CT examination for distant metastasis and regional lymph node metastasis in colorectal cancer.

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.