Sentinel Lymph Node Metastasis Research Articles

Evaluation of RASSF1A methylation in the lysate of sentinel lymph nodes for detecting breast cancer metastasis: A diagnostic accuracy study.

The restriction enzyme-based digital methylation-specific polymerase chain reaction (RE-dMSP) assay is useful for diagnosing sentinel lymph node (SN) metastasis in patients with breast cancer, by detecting tumor-derived methylated Ras association domain-containing protein 1 (RASSF1A). In addition, this assay has high concordance (95.0%) with one-step nucleic acid amplification (OSNA). The present study aimed to perform RE-dMSP using OSNA lysate from more patients and to re-evaluate its clinical usage. Overall, 418 SNs from 347 patients were evaluated using both OSNA and RE-dMSP. The concordance rate was 83.3% (348/418). RASSF1A methylation of the primary tumors was negative in 36 patients. When these patients were excluded, the concordance rate improved to 88.2% (330/374). Of the 79 OSNA-negative cases, 19 were RE-dMSP-positive, although all were positive for cytokeratin 19 expression in the primary tumor, suggesting that RE-dMSP can detect tumor-derived DNA with a higher sensitivity. The percent of methylated reference of the breast tumors showed a wide variety in the 16 OSNA-positive/RE-dMSP-negative cases, and such variability of methylation could have affected the results in these patients. In conclusion, although RE-dMSP can diagnose SN metastasis with high sensitivity and accuracy, and can be a supplementary tool to OSNA in breast cancer, RE-dMSP showed certain discordance with OSNA and critically depended on the absence or heterogeneity of DNA methylation in breast tumors. Further research is expected to develop an assay targeting other DNA alterations, such as mutations.

Relaxivity Enhancement of Hybrid Micelles via Modulation of Water Coordination Numbers for Magnetic Resonance Lymphography.

Considerable efforts have been made to develop nanoparticle-based magnetic resonance contrast agents (CAs) with high relaxivity. The prolonged rotational correlation time (τR) induced relaxivity enhancement is commonly recognized, while the effect of the water coordination numbers (q) on the relaxivity of nanoparticle-based CAs gets less attention. Herein, we first investigated the relationship between T1 relaxivity (r1) and q in manganese-based hybrid micellar CAs and proposed a strategy to enhance the relaxivity by increasing q. Hybrid micelles with different ratios of amphiphilic manganese complex (MnL) and DSPE-PEG2000 were prepared, whose q values were evaluated by Oxygen-17-NMR spectroscopy. Micelles with lower manganese doping density exhibit increased q and enhanced relaxivity, corroborating the conception. In vivo sentinel lymph node (SLN) imaging demonstrates that DSPE-PEG/MnL micelles could differentiate metastatic SLN from inflammatory LN. Our strategy makes it feasible for relaxivity enhancement by modulating q, providing new approaches for the structural design of high-performance hybrid micellar CAs.

Development and validation of convolutional neural network-based model to predict the risk of sentinel or non-sentinel lymph node metastasis in patients with breast cancer: a machine learning study

For patients with sentinel lymph node (SLN) metastasis and low risk of residual non-SLN (NSLN) metastasis, axillary lymph node (ALN) dissection could lead to overtreatment. This study aimed to develop and validate an automated preoperative deep learning-based tool to predict the risk of SLN and NSLN metastasis in patients with breast cancer (BC) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images. In this machine learning study, we retrospectively enrolled 988 women with BC from three hospitals in Zhejiang, China between June 1, 2013 to December 31, 2021, June 1, 2017 to December 31, 2021, and January 1, 2019 to June 30, 2023, respectively. Patients were divided into the training set (n=519), internal validation set (n=129), external test set 1 (n=296), and external test set 2 (n=44). A convolutional neural network (CNN) model was proposed to predict the SLN and NSLN metastasis and was compared with clinical and radiomics approaches. The performance of different models to detect ALN metastasis was measured by the area under the curve (AUC), accuracy, sensitivity, and specificity. This study is registered at ChiCTR, ChiCTR2300070740. For SLN prediction, the top-performing model (i.e., the CNN algorithm) achieved encouraging predictive performance in the internal validation set (AUC 0.899, 95% CI, 0.887-0.911), external test set 1 (AUC 0.885, 95% CI, 0.867-0.903), and external test set 2 (AUC 0.768, 95% CI, 0.738-0.798). For NSLN prediction, the CNN-based model also exhibited satisfactory performance in the internal validation set (AUC 0.800, 95% CI, 0.783-0.817), external test set 1 (AUC 0.763, 95% CI, 0.732-0.794), and external test set 2 (AUC 0.728, 95% CI, 0.719-0.738). Based on the subgroup analysis, the CNN model performed well in tumour group smaller than 2.0cm, with the AUC of 0.801 (internal validation set) and 0.823 (external test set 1). Of 469 patients with BC, the false positive rate of SLN prediction declined from 77.9% to 32.9% using CNN model. The CNN model can predict the SLN status of any detectable lesion size and condition of NSLN in patients with BC. Overall, the CNN model, employing ready DCE-MRI images could serve as a potential technique to assist surgeons in the personalized axillary treatment of in patients with BC non-invasively. National Key Research and Development projects intergovernmental cooperation in science and technology of China, National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province, and Zhejiang Medical and Health Science Project.

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients

ObjectiveInternal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. MethodsA total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. ResultsThe overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. ConclusionOur nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Indications for sentinel lymph node biopsy in node-negative oral cancers.

We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes. The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome. In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%. SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control.

Contribución de la medicina nuclear en la cirugía de precisión en el cáncer de mama

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT1-2 tumors without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumors, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18F-FDG PET/CT in an effort to tailor systemic and loco regional treatment.

Effective treatment of metastatic sentinel lymph nodes by dual-targeting melittin nanoparticles

Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial for patient staging and prognosis. However, the simultaneous diagnosis of metastasis and the implementation of imaging-guided SLN therapy is challenging. Here, we report a melittin-loaded and hyaluronic acid (HA)-conjugated high-density lipoprotein (HDL) mimic phospholipid scaffold nanoparticle (MLT-HA-HPPS), which dually-target to both breast cancer and its SLN and efficiently inhibit SLN metastasis in the LN metastasis model. The melittin peptide was successfully loaded onto HA-HPPS via electrostatic interactions, and MLT-HA-HPPS possesses effective cytotoxicity for breast cancer 4T1 cells. Moreover, the effective delivery of MLT-HA-HPPS from the primary tumor into SLN is monitored by NIR fluorescence imaging, which greatly benefits the prognosis and treatment of metastatic SLNs. After paracancerous administration, MLT-HA-HPPS can efficiently inhibit primary tumor growth with an inhibition rate of 81.3% and 76.5% relative to the PBS-treated control group and HA-HPPS group, respectively. More importantly, MLT-HA-HPPS can effectively inhibit the growth of the metastatic SLNs with an approximately 78.0%, 79.1%, and 64.2% decrease in SLNs weight than those in PBS, HA-HPPS, and melittin-treated mice, respectively. Taken together, the MLT-HA-HPPS may provide an encouraging theranostic of SLN drug delivery strategy to inhibit primary tumor progression and prevent SLN metastasis of breast cancer.Graphical

Dual-targeting lanthanide-ICG-MOF nanoplatform for cancer Theranostics: NIR II luminescence imaging guided sentinel lymph nodes surgical navigation.

Sentinel lymph node imaging is important for breast tumor staging and prediction of postoperative metastasis. However, clinical sentinel lymph node imaging has limitations such as low specificity, low contrast, and short retention time. The combination of bio-conjugates chemistry and luminescence technology may achieve the specific targeting effect. In this research, we designed a dual-targeting composite nanoprobe (∼50nm) using a metal-organic framework (MOF) as carrier, loaded with lanthanide and ICG, and combined with hyaluronic acid and folic acid to detect metastatic lymph nodes. The coupled hyaluronic acid and folic acid can target to the tumor cells and dentritic cells with a dual-targeting effect. The FA-HA/ZIF-8@ICG nanoprobes can accumulate rapidly in sentinel lymph node with a stronger luminescence intensity (1.6 times) than that of normal popliteal lymph nodes in vivo, thus distinguish metastatic sentinel lymph node from normal effectively. Furthermore, due to the MOF carrier, the integrated lanthanide and near-infrared dye by transferring the absorbed excitation energy from ICG to Nd3+ can enhance the signal-to-background ratio of NIR II imaging and have long retention time in vivo imaging. Finally, the FA-HA/ICG@Ln@ZIF-8 nanoplatform increased the penetration depth and contrast of imaging, prolonged the retention time, and achieved the sentinel lymph nodes surgical resection. This study has important implications for lymph node imaging and surgical navigation.

Diagnostic value of contrast-enhanced ultrasound for sentinel lymph node metastasis in breast cancer: an updated meta-analysis.

The status of sentinel lymph nodes (SLN) is an important factor in determining the stage of breast cancer (BC) and the surgical procedure, and also a biomarker of the BC prognosis. This meta-analysis was performed to investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) for SLN metastasis. A systematic search was conducted for relevant articles published in the PubMed, Embase, Web of Science, OVID databases, and Cochrane Library from inception to March 2023. We calculated the sensitivity, specificity, positive and negative likelihood ratio (PLR; NLR), diagnostic odds ratio (DOR), and summary receiver operator characteristic (SROC) curve to evaluate the diagnostic efficacy of CEUS in SLN metastasis. Subgroup analysis was also performed to investigate potential sources of heterogeneity. A total of 12 studies with 1525 patients were included in this meta-analysis. The overall pooled sensitivity and specificity of CEUS in the diagnosis of SLN metastasis were 0.91 (95% CI: 0.84-0.95) and 0.86 (95% CI: 0.78-0.92). The PLR, NLR, and DOR were 6.51 (95% CI: 4.09-10.36), 0.11 (95% CI: 0.07-0.18), and 59.43 (95% CI: 33.27-106.17), respectively, and the area under the SROC curve was determined to be 0.95 (95%CI: 0.92-0.96), all showing excellent diagnostic value. In the subgroup analysis, percutaneous CEUS was more sensitive than intravenous CEUS in the diagnosis of SLN metastases (0.92 versus 0.82, p < 0.05). CEUS, especially percutaneous CEUS, is a reliable imaging technique for diagnosing SLN metastasis and providing important information in the stage management of breast cancer.

A nanoparticle composed of totally hospital-available drugs and isotope for fluorescence/SPECT dual-modal imaging-guided photothermal therapy to inhibit tumor metastasis

As primary sites of tumor metastasis, sentinel lymph nodes (SLNs) require a highly biocompatible theranostic platform for precise localization and treatment to inhibit tumor metastasis. Herein, indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were fabricated by ICG-induced self-assembly and radiolabeled with technetuim-99 m (99mTc). The fabricated NPs were composed of hospital-available drugs and isotopes, making them highly biocompatible for in vivo applications. In a mouse model of SLN metastasis, the prepared NPs exhibited excellent capacity for preoperative planning by single-photon emission computed tomography (SPECT) imaging-enabled SLN localization, near-infrared fluorescence (NIRF) imaging-enabled intraoperative real-time monitoring, and SLN photothermal treatment. Photothermal treatment with SLN enhanced the inhibition of lung metastasis and significantly increased the survival time of mice. The prepared NPs were highly biocompatible and exhibited efficient theranostic properties for inhibiting cancer metastasis, making them promising candidates for clinical translation.

Consistent Learning-Based Breast Tumor Segmentation and Its Application in Sentinel Lymph Node Metastasis Prediction.

Accurate staging of lymph nodes provides crucial diagnostic information for breast cancer patients, where segmentation is of great importance by localizing and visualizing the breast tumor of interest. Nevertheless, current segmentation methods perform average when facing large span of tumor sizes, degraded image quality, blurred tumor boundaries, and resulting noise during manual annotation. Therefore, we develop a Multi-scale RepVGG-based Segmentation Network (MPSegNet) to segment breast tumor from MR images. In particular, we construct a consistent learning framework for the MPSegNet to alleviate the impact of noisy labels upon segmentation results. The rationale is that different views covering the same breast tumors are supposed to generate identical segmentation predictions. Then, we predict SLN metastasis given segmented breast tumors, where we evaluate the relationships between the predictive performance and tumor segmentations under different consistencies. The results show the superiority of our method over other state-of-the-art methods. A high consistency among multiple views can boost the segmentation performance during consistent learning. However, the optimal segmentation does not produce the best SLN metastatic prediction results, implying that the dependence of classification upon segmentation needs to be elaborately investigated further.Clinical Relevance- This study facilitates more accurate segmentation of breast tumors with consistent learning, and provides an initial analysis between tumor segmentation and subsequent prediction of SLN metastasis, which has potential significance for the precise medical care of breast cancer patients.

Cancer cell-derived extracellular vesicles drive pre-metastatic niche formation of lymph node via IFNGR1/JAK1/STAT1-activated-PD-L1 expression on FRCs in head and neck cancer

ObjectiveThe aim of this study is to evaluate the role of FRCs regulated by cancer cell-derived extracellular vesicles (CEVs) played in pre-metastatic niche (PMN) formation of lymph node (LN). Materials and methodsThe FRCs in sixty fresh cervical LNs from 20 patients were evaluated by flow cytometric analysis. Cells in LN with or without metastasis were analyzed by single-cell RNA sequencing (scRNA-seq). CEVs were isolated from the culture supernatant of primarily cultured cancer cells and cocultured with FRCs. Mass Spectrometry was used to identify LN metastasis related protein in CEVs. The activation of IFNGR1/JAK1/STAT1-activated-PD-L1 pathway in FRCs was detected by western blotting. FRCs were co-cultured with CD8+ T lymphocytes to confirm the cytotoxicity assay of FRCs. ResultsThe proportion of fibroblastic reticular cells (FRCs) was significantly higher in micro-metastatic LN in head and neck squamous cell carcinoma patients (HNSCC, p < 0.05) and scRNA-seq analysis further showed a high focus of extracellular vesicles-related pathway on FRCs in LN with metastasis (p < 0.05). Interferon gamma receptor 1 (IFNGR1) in CEVs can be engulfed by FRCs and promote PD-L1 expression on FRCs via JAK1-STAT1 pathway, resulting in an increased CD8+ T cell exhaustion. ConclusionIFNGR1, originated from cancer cell-derived extracellular vesicles, promote PD-L1 expression on FRCs and subsequent CD8+ T cell exhaustion via JAK1-STAT1 activation, which facilitate pre-metastatic niche formation and tumor metastasis in sentinel lymph node in HNSCC.

Extremely Low Incidence of Local-Regional Recurrences Observed Among T1-2 N1 (1 or 2 Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy Without Completion Axillary Node Dissection.

Completion axillary node dissection (CLND) is routinely omitted in cT1-2 N0 breast cancer treated with upfront, breast-conserving therapy and sentinel node biopsy (SLNB) showing one to two positive sentinel nodes (SLNs). The purpose of this study was to determine the incidence and impact of axillary treatment among patients treated with mastectomy in a contemporary cohort. A prospective, institutional database was reviewed from 2006 to 2015 to identify patients with T1-2 breast cancer treated with upfront mastectomy and SLNB found to have one to two positive SLNs. Patients were stratified by axillary therapy [including CLND and/or post-mastectomy radiation therapy (PMRT)], and clinicopathologic factors and incidence rates of local-regional and distant recurrence were analyzed. A total of 548 patients were identified, including 126 (23%) without CLND. Rates of PMRT were similar between those with and without CLND (35.3% vs. 28.6%, p = 0.16). On multivariate analysis, two rather than one positive SLN, larger SLN metastasis size, frozen-section analysis of the SLNB, and adjuvant chemotherapy were significantly associated with receipt of CLND. At a median follow-up of 7 years, there were only two local-regional recurrences in the no-CLND group, of which only one was an axillary recurrence. The 5-years incidence rate of LRR was not significantly different for those with and without CLND (1.3% vs. 1.8%, p = 0.93). We found extremely low rates of local-regional recurrence among those with T1-2 breast cancer undergoing upfront mastectomy with 1-2 positive SLNs. Further axillary surgery may not be indicated in selected patients treated with a multidisciplinary approach, including adjuvant therapies.

Nuclear medicine contribution to precision surgery in breast cancer

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT 1-2 tumours without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumours, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18F-FDG PET/CT in an effort to tailor systemic and loco regional treatment.

An Australian-based nomogram predicting nodal positivity for breast cancer in older patients

IntroductionRegional nodal status is one of the most powerful prognosticators in breast cancer. The sentinel lymph node biopsy (SLNB) evaluates the first node in the axillary lymphatic basin theorised to drain the anatomical region of breast cancer. Recent literature has appropriately raised the query of the need for SLNB for breast cancer in older patients (BCOP). Though some early-stage older patients may safely have SLNB omitted, we are potentially missing the under-represented aggressive cancers. No sentinel lymph node metastases nomogram has been developed solely from BCOP data to date. This study aimed to identify older patients with breast cancer at risk for nodal involvement using a nomogram developed from their data alone. MethodsA retrospective analysis of prospectively collected data on BCOP (aged ≥70 years) was performed using the Breast Surgery Quality Audit (BQA). Inclusion criteria were T1-2 invasive breast cancer patients that underwent a SLNB from 1st January 2001 to 31st December 2019. The primary outcome was nodal involvement. Data obtained from the dataset included: age, tumour type, tumour size in millimeters, histological grade, lymphovascular invasion, oestrogen receptor status, progesterone receptor status, HER2 status and referral source. Binary logistic regression was used to develop a nomogram. The model was internally validated by splitting the data set (80% for training and 20% for testing). A receiver operating characteristic curve was developed, with the area under the curve (AUC) and a calibration plot. ResultsThere were 22,313 patients of which 14,856 (66.6%) were symptomatic presentations and 7457 (33.4%) were screen-detected. Invasive tumour type, tumour size, tumour grade, lymphovascular invasion, oestrogen receptors, and referral source indicated a statistically significant effect on predicting a nodal positivity event (Table 1). The AUC was 0.782 (95% CI 0.776–0.789) (Fig. 1a) and demonstrated good calibration (Fig. 1b). The negative predictive value established was 85%. ConclusionWe have developed an Australian sentinel lymph node metastasis nomogram for BCOP using routine histopathological data obtained pre-operatively (Fig. 2). This is the first Australian nomogram, as well as the first nomogram developed solely for BCOP – and maintains a superior AUC compared to other well-established nomograms.

Risk Factors Associated With Sentinel Lymph Node Metastasis in Clinically Node-Negative Breast Cancer.

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node negative breast cancer. If predictive factors for sentinel lymph node (SLN) metastasis could be identified, it would allow selection of candidates for SLNB and omit axillary surgery in those with the lowest risk of axillary lymph node involvement. The aim of this study was to determine risk factors associated with SLN metastasis in breast cancer patients in Bahrain. Patients with clinically node-negative breast cancer who underwent SLNB at a single institution between 2016 and 2022 were identified from the pathology database. Patients who had failure of localization of SLN, those with bilateral cancers and those treated for a local recurrence were excluded. A total of 160 breast cancer patients were retrospectively analyzed. Of these, 64.4% had a negative SLNB and 21.9% of all cases underwent axillary dissection. The following parameters emerged as predictors of SLN metastasis in univariate analysis: age; tumour grade; ER status; presence of lymphovascular invasion (LVI) and tumor size. On multivariate analysis, age was not independently associated with the incidence of SLN metastasis. This study showed that high tumour grades, presence of LVI and large tumour size were all risk factors related to axillary metastasis after SLNB in breast cancer. In the elderly, the incidence of SLN metastasis appeared to be relatively low, providing an opportunity to de-escalate axillary surgery in these patients. These findings may allow for the development of a nomogram to estimate the risk of SLN metastasis.

Predictors of Sentinel Lymph Node Metastasis in Very Thin Invasive Melanomas.

Melanomas <0.8 mm in Breslow depth have less than 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve outcomes for these patients. To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas. The National Cancer Database was reviewed from 2012 to 2018 for melanoma patients with Breslow thickness < 0.8 mm. Data were analyzed between July 7, 2022, through February 25, 2023. Patients were excluded if data regarding their ulceration status or sentinel lymph node biopsy (SLNB) performance were unknown. We analyzed patient, tumor, and health system factors for their effect on SLN positivity. Data were analyzed using chi-square tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses. Positive nodal metastases were seen in 876 (5.0%) of patients who underwent sentinel lymph node biopsy (17,692). Factors significantly associated with nodal positivity on multivariable analysis include: lymphovascular invasion (Odds ratio (OR)= 4.5, p< 0.001), ulceration (OR= 2.6, p < 0.001), mitoses (OR= 2.1, p< 0.001), and nodular subtype (OR= 2.1, p< 0.001). Five-year overall survival was 75% and 92% for patients with positive and negative SLN, respectively. Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumor factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from sentinel lymph node biopsy.

An improved nomogram including elastography for the prediction of non-sentinel lymph node metastasis in breast cancer patients with 1 or 2 sentinel lymph node metastases.

The rate of breast-conserving surgery is very low in China, compared with that in developed countries; most breast cancer patients receive mastectomy. It is great important to explore the possibility of omitting axillary lymph node dissection (ALND) in early-stage breast cancer patients with 1 or 2 positive sentinel lymph nodes (SLNs) in China. The aim of this study was to develop a nomogram based on elastography for the prediction of the risk of non-SLN (NSLN) metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. A total of 601 breast cancer patients were initially recruited. According to the inclusion and exclusion criteria, 118 early-stage breast cancer patients with 1 or 2 positive SLNs were finally enrolled and were assigned to the training cohort (n=82) and the validation cohort (n=36), respectively. In the training cohort, the independent predictors were screened by logistic regression analysis and then were used to conducted the nomogram for the prediction of NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The calibration curves, concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Decision curve analysis (DCA) were used to verified the performance of the nomogram. The multivariable analysis showed that the enrolled patients with positive HER2 expression (OR=6.179, P=0.013), Ki67≥14% (OR=8.976, P=0.015), larger lesion size (OR=1.038, P=0.045), and higher Emean (OR=2.237, P=0.006) were observed to be the independent factors of NSLN metastasis. Based on the above four independent predictors, a nomogram was conducted to predict the risk of the NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The nomogram showed good discrimination in the prediction of NSLN metastasis, with bias-corrected C-index of 0.855 (95% CI, 0.754-0.956) and 0.853 (95% CI, 0.724-0.983) in the training and validation cohorts, respectively. Furthermore, the AUC was 0.877 (95%CI: 0.776- 0.978) and 0.861 (95%CI: 0.732-0.991), respectively, indicating a good performance of the nomogram. The calibration curve suggested a satisfactory agreement between the predictive and actual risk in both the training (χ2 = 11.484, P=0.176, HL test) and validation (χ2 = 6.247, p = 0.620, HL test) cohorts, and the obvious clinical nets were revealed by DCA. We conducted a satisfactory nomogram model to evaluate the risk of NSLN metastasis in early-stage breast cancer patients with 1 or 2 SLN metastases. This model could be considered as an ancillary tool to help such patients to be selectively exempted from ALND.

Gene expression comparison between primary aggressive luminal breast cancer and paired axillary and sentinel lymph node metastasis.

e13060 Background: More aggressive and therapy-resistant hormone receptor (HR)-positive breast cancer (hereafter luminal breast cancer, LBC) remains a great challenge. Few studies examine the genomics of axillary lymph node (ALN) metastasis in LBC. The aim of this study was to characterize and compare the mRNA expression patterns of primary breast cancers and paired ALN metastases. Methods: Aggressive pT1-2N2-3M0 LBC patients aged over 18 years who were treated at Shandong Provincial Hospital Affiliated to Shandong First Medical University and had available matched primary and metastatic tumor samples for gene expression analyses were retrospectively recruited. Bulk mRNA expression levels were determined by RNA sequencing (Illumina NovaSeq 6000 system) and calculated using featureCounts. Differential gene expression analysis was performed using DESeq2. All analyses were carried out with differentially expressed genes (DEGs) with an FDR &lt;0.05. Changes of intrinsic subtypes from primary to metastatic disease were assessed. Results: Ten LBC patients with paired tumor samples were included. Compared with the primary tumor, ALN metastatic tumor had 1509 statistically significant DEGs, including 743 upregulated genes and 766 downregulated genes. Notably, there was an upregulation of genes related to immune response-activating signal transduction, T cell receptor signaling pathway, B cell receptor signaling pathway, and cytokine-cytokine receptor interaction in the ALN metastasis. The downregulation of genes were mainly enriched in the PI3K-Akt signaling pathway, ECM-receptor interaction, Wnt signaling pathway, and TGF-beta signaling pathway. Intrinsic subtype distribution in primary tumors was different from those in ALN metastatic tumors, such as Luminal A (30% vs. 50%), Luminal B (10% vs. 20%), HER2-enriched (20% vs. 10%), Basal-like (10% vs. 10%), and Normal-like (30% vs. 10%). These results suggest that LBC is a highly heterogeneous disease. Conclusions: In aggressive pT1-2N2-3M0 LBC, ALN metastases have a distinct gene expression profile and show upregulation of immune-related genes ( CR2, BLK, PAX5, CD19, FCRL1, TNFRSF13B). Genes associated with signaling pathways are involved in the development of breast cancer ( FST, TNN, LAMC3, SFRP2, FGF18), and are downregulated when compared to autologous primary cancer. These pathways are potential targeted pathways in the treatment of breast cancer. LBC cells metastatic to lymph nodes undergo a change to metastasize and survive in the new microenvironment, which may provide insights into the metastatic process. Besides, a switch towards more aggressive intrinsic subtype from primary to advanced disease is also observed.

Diagnosing sentinel lymph node metastasis of T1/T2 breast cancer with conventional ultrasound combined with double contrast-enhanced ultrasound: a preliminary study.

In patients with T1/T2 breast cancer (BC), sentinel lymph node (SLN) status is essential for prognosis and treatment. This study investigated the value of conventional ultrasound combined with double contrast-enhanced ultrasound in diagnosing the metastasis of SLNs in patients with T1/T2 BC. This study employed a prospective design (this diagnostic study was not registered on a clinical trial platform), and the participants formed a convenience series. Based on the inclusion and exclusion criteria, 163 patients with BC who received treatment in the First Affiliated Hospital of Soochow University from July 2017 to December 2021 were included in this study. A total of 165 SLNs from 163 patients with T1/T2 BC were analyzed. All patients underwent percutaneous contrast-enhanced ultrasound (PCEUS) to trace SLNs before the operation. Subsequently, all patients underwent conventional ultrasound and intravenous contrast-enhanced ultrasound (ICEUS) examinations to observe the SLNs. The results of the conventional ultrasound, ICEUS, and PCEUS of the SLNs were analyzed. The associations between the risk of SLN metastasis and imaging features were evaluated via a nomogram based on the pathological results. Overall, 54 metastatic SLNs and 111 nonmetastatic SLNs were evaluated. Metastatic SLNs displayed a greater cortical thickness, area ratio, eccentric fatty hilum, and hybrid blood flow on conventional ultrasound compared with nonmetastatic SLNs (P<0.001). According to PCEUS, 75.93% of metastatic SLNs showed heterogeneous enhancement (type II and III), and 73.88% of nonmetastatic SLNs showed homogeneous enhancement (type I; P<0.001). According to ICEUS, heterogeneous enhancement (type B/C, 20.37% vs. 11.71%) and overall enhancement (55.56% vs. 23.42%) were more common in metastatic SLNs than in nonmetastatic SLNs (P<0.001). Logistic regression analysis showed that the cortical thickness and enhancement type of PCEUS were independent predictors of SLN metastasis. Moreover, a nomogram combining these factors showed a high diagnostic ability for SLN metastasis (unadjusted concordance index 0.860, 95% CI: 0.730-0.990; bootstrap-corrected concordance index 0.853). The nomogram of cortical thickness and enhancement type of PCEUS could effectively diagnose SLN metastasis in patients with T1/T2 BC.