Exempting axillary staging surgery in breast cancer using multimodal ultrasound imaging and radiomics of sentinel lymph nodes.

To explore the clinical efficiency of using the sentinel lymph node (SLN) imaging agent 99mTc-rituximab for lymphoscintigraphy and SLN biopsy (SLNB) in oral squamous cell carcinoma (OSCC) patients. A retrospective study was conducted on 23 patients with OSCC who underwent 99mTc-rituximab lymphoscintigraphy and SLNB. The cohort comprised 16 men (69.6%) and 7 women (30.4%) with a median age of 64.0 years (range: 33-90years). All patients received a preoperative peritumoral injection of 99mTc-rituximab. The SLN detection rates (SDRs) of SLN imaging and SLNB were analyzed. The localizations of SLNs were counted. Patients were followed up after surgery. Differences were considered significant for a p-value of less than 0.05. The SDRs of lymphoscintigraphy and SLNB were 91.3% (21/23) and 100.0% (23/23), respectively. The SDRs of lymphoscintigraphy for patients in pathological stages I/II and III/IVa were 100.0% (15/15) and 75.0% (6/8), respectively. Among the 2 patients with negative imaging results, both were stage IVa and both had SLN metastasis. The SLNs were located in levels Ib, IIa, IIb, III, and IV, accounting for 45.0% (18/40), 40.0% (16/40), 10.0% (4/40), 2.5% (1/40), and 2.5% (1/40), respectively. The median follow-up duration was 32.0months (range: 13.0-68.0months). During follow-up, none of the 23 patients (100.0%) showed lymph node (LN) metastasis. As a result, the sensitivity, negative predictive value (NPV), and accuracy were all 100.0%. The application of 99mTc-rituximab for SLN imaging and SLNB in OSCC patients demonstrated high detection rates and accuracy, holding significant clinical value.

Accurate sentinel lymph node (SLN) characterization is essential for breast cancer management, prompting advancements in imaging technologies such as contrast-enhanced ultrasound (CEUS) and sound touch quantification (STQ) to enhance diagnostic precision. To explore the value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of sentinel lymph node (SLN) in breast cancer. A total of 91 breast cancer patients (91 SLNs) admitted to the hospital from February 2022 to December 2023 were selected for this study. Among them, 26 patients with metastatic SLN confirmed by surgery and pathology were included in the metastatic SLN group, and 65 patients with non-metastatic SLN were included in the non-metastatic SLN group. Preoperative examination results of CEUS and STQ were retrospectively analyzed. The diagnostic efficacy of perfusion characteristics evaluated by CEUS and STQ parameters for the properties of SLN in breast cancer was analyzed using the receiver operating characteristics (ROC) curve. Statistical methods such as chi-square tests and logistic regression analysis were employed to analyze the data. Enhancement patterns differed significantly between the metastatic SLN and non-metastatic SLN groups (p< 0.05). ROC curve analysis indicated that CEUS perfusion characteristics had an AUC value of 0.823 for diagnosing SLN properties, with a sensitivity of 84.62% and specificity of 70.77% using type I as the critical value. Additionally, STQ measurement showed significantly higher values in the metastatic SLN group (44.18 ± 6.53 kPa) compared to the non-metastatic SLN group (34.69 ± 6.81 kPa) (t= 6.075, p< 0.001). The AUC value for STQ parameters in diagnosing metastatic SLN was 0.849, with a sensitivity of 73.08% and specificity of 92.31% using 42.40 kPa as the critical value. Though the AUC value of STQ measurement was higher than CEUS perfusion characteristics alone, the difference was not statistically significant (Z= 0.393, p= 0.695). Moreover, combining CEUS perfusion characteristics with STQ parameters yielded an AUC value of 0.815 for diagnosing SLN properties, showing no significant difference compared to diagnosis with CEUS or STQ parameters alone (Z= 0.149, 0.516, p= 0.882, 0.606). Combined use of perfusion characteristics evaluated by CEUS and STQ parameters can significantly improve the diagnostic specificity of SLN in breast cancer. It is worthy of clinical promotion.

The Clinical Value of Hybrid Sentinel Lymphoscintigraphy to Predict Metastatic Sentinel Lymph Nodes in Breast Cancer

This meta-analysis aims to determine the accuracy of contrast-enhanced ultrasonography (CEUS) in the qualitative diagnosis of metastatic sentinel lymph node (SLN) for patients with breast cancer. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the STATA software, version 12.0 (Stata Corp, College Station, TX, USA). We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR + /LR-), diagnostic odds ratio (DOR) and receiver operating characteristic (SROC) curve. Thirteen articles that met all inclusion criteria were included in this meta-analysis. A total of 876 breast cancer patients were assessed, including 372 patients with metastatic SLN and 504 patients without metastatic SLN. All SLN were histologically confirmed after conducting CEUS. The pooled Sen was 0.80 (95%CI = 0.76-0.84); the pooled Spe was 0.94 (95% CI = 0.91-0.96). The pooled LR + was 6.28 (95%CI = 3.61-10.92); the pooled negative LR - was 0.218 (95% CI = 0.10-0.31). The pooled DOR of CEUS in qualitative diagnosis of SLN metastasis was 49.10 (95% CI = 27.89-86.45). The area under the SROC curve was 0.937 (standard error [SE] =0.0128). Our meta-analysis suggests that CEUS may have high a diagnostic accuracy in testing for metastatic SLN in breast cancer. Thus, CEUS may be a good tool for differential diagnosis between metastatic and non-metastatic SLN.

To investigate the significance of preoperative contrast-enhanced ultrasound (CEUS) coupled with injections of methylene blue (MB) into the lymph nodes, alongside intracutaneous injections of indocyanine green (ICG) for sentinel lymph node (SLN) identification in early breast cancer. All patients from a single institution were prospectively randomized into two groups: CEUS Group (preoperative SLN-CEUS coupled with injections of MB into the lymph nodes, with ICG intracutaneous injections for SLN identification during surgery) and Blue Staining Group (intracutaneous injections of both ICG and MB for SLN mapping during surgery). Pathological results served as the gold standard. Multivariate logistic regression analysis was used to identify independent risk factors for SLN metastasis. Areas under the receiver-operating characteristic curve (AUC) were used to evaluate the ability of CEUS to diagnose SLN metastasis. 134 patients were enrolled (CEUS Group: 76 patients, Blue Staining Group: 58 patients). CEUS Group achieved a 100.0% success rate in detecting SLNs, with identifying a median of 1 SLN, while Blue Staining Group identifying a median of 4 SLNs per case (p < 0.001). CEUS enhancement pattern was the only factor independently linked to SLN metastasis (p < 0.001), showing a sensitivity of 90.5% and a specificity of 94.5%. The AUC for identifying SLN metastasis was 0.925. CEUS enhancement pattern is helpful to determine the SLN metastasis. Preoperative CEUS, combined with MB injections into lymph nodes and intracutaneous ICG injections during surgery, provides a reliable method for localizing SLNs. This approach minimizes the risk of non-SLNs excisions. Question Despite the critical role of sentinel lymph node (SLN) detection in surgical outcomes, current preoperative imaging-guided SLN tracing remains in the exploratory stage. Findings Contrast-enhanced (CE) US achieved 100% SLN detection success with fewer non-target lymph nodes excised versus blue dye, demonstrating superior sensitivity and specificity metastatic prediction. Clinical relevance Preoperative SLN-CEUS, combined with intralymphatic methylene blue injection and intracutaneous indocyanine green administration during surgery, enables precise SLN identification and metastasis prediction. This approach minimizes the risk of unnecessary non-SLN resection during SLNB.

A new approach to pre-treatment assessment of the N 0 neck in oral squamous cell carcinoma: the role of sentinel node biopsy and positron emission tomography

Objective: To explore the preoperative evaluation of sentinel lymph node (SLN) biopsy using contrast-enhanced ultrasonography (CEUS) in early breast cancer patients and the involved disturbing factors. Methods: Eighty-three female early breast cancer patients who underwent concurrent surgery in the Affiliated Cancer Hospital of Zhengzhou University between January 2017 and May 2018 were enrolled. CEUS was used to seek SLN and determine lymph node metastasis after signature of preoperative informed consent. Rapid pathological examination was used to determine whether metastasis existed in SLN. The sensitivity, specificity, accuracy, the differences between CEUS and pathological results, and the involved disturbing factors were evaluated. Results: A total of 212 SLNs were detected by CEUS and SLN biopsy with an average of 2.6 SLNs detected per patient, including 39 SLNs with cancer metastasis (18.4%) and 173 SLNs without cancer metastasis (81.6%). Among the 83 patients, 29 patients were predicted SLN-positive preoperatively utilizing CEUS (including 21 cases with SLN pathological metastasis and 8 cases with non-metastasis), 54 patients were predicted SLN-negative (including 5 cases with SLN pathological metastasis and 49 cases with non-metastasis). The preoperative evaluation of SLN utilizing CEUS were performed with a sensitivity of 80.8% (21/26), specificity of 86.0% (49/57), positive predictive value of 72.4% (21/29), and negative predictive value of 90.7% (49/54), positive likelihood ratio of 5.75, negative likelihood ratio of 0.22, and the accuracy of 84.3% (70/83), respectively. The area under the ROC curve (AUC) was 0.834 (95% CI: 0.736-0.906). The primary tumor mean size of SLN-negative group predicted preoperatively utilizing CEUS was (1.78±0.14) cm, and that of the SLN positive group was (2.64±0.19) cm. The difference between the two groups was (0.86±0.24) cm with statistical significance (P=0.000 6). The SLN mean size of SLN-negative group (141 SLNs) was (1.41±0.05) cm and that of SLN-positive group (71 SLNs) was (1.69±0.07) cm. The difference between the two groups was (0.28±0.09) cm with statistical significance (P=0.002 8). Conclusions: Preoperative CEUS possesses the predictive value for SLN metastasis in early breast cancer. The predicted results may be influenced by the primary tumor size and the SLN size.

Benign as well as malignant tumour tissues of the breast demonstrate higher fluorescence intensity (FI) than normal breast tissue after application of a photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic sentinel and axillary lymph nodes in patients with breast cancer. In all, 11 patients received 30 mg 5-aminolevulinic acid (ALA) kg−1 bodyweight orally 3 h prior to surgery. The sentinel lymph node was marked with Nanocoll® preoperatively and with a blue dye intraoperatively. Tumour excision, excision of the sentinel lymph node and an axillary lymph node dissection were performed during the same surgical session. The operation site was illuminated with blue light (400 nm) to obtain macroscopic tissue characterisation of fluorescence. Tissue samples were stored protected from light, and analysed using a fluorescence microscope. Results were correlated with histopathology. In all, 14 sentinel lymph nodes, seven axillary lymph nodes and seven primary tumours were analysed. Metastatic sentinel lymph nodes demonstrated a statistically significant higher FI than nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary tumour were comparably high, and were statistically significantly higher compared to the normal mammary tissue. Intraoperatively, only in a few cases, it was possible to recognise the metastatic sentinel lymph node macroscopically with blue light. Our study indicates that photodynamic diagnosis with ALA has a potential in the diagnosis and detection of the sentinel lymph node in patients with breast cancer, and is worth to be further investigated and developed for intraoperative photodynamic diagnosis and possibly therapy.

Objective: This self-controlled study aimed to investigate the feasibility of substituting indocyanine green (ICG) for radioisotope (RI) for combined imaging of axillary sentinel lymph node (SLN) in breast cancer. Study Design: Primary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary SLNB. The main observation indices was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indices were the axillary SLN detection rate, mean number of axillary SLN detected, mean number of metastatic axillary SLN detected and safety.Result: All 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (P&amp;gt;0.05). The mean number of axillary SLN detected was significantly higher with ICG+MB than with RI+MB (4.99±2.42 vs. 4.02±2.33, P&amp;lt;0.001). No tracer-related adverse events occurred.Conclusion: ICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer. Citation Format: Yuting Jin, Long Yuan, Jun Jiang, Xiaowei Qi. A prospective self-controlled study of indocyanine green instead of radioisotope for axillary sentinel lymph nodes in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-13.

Accurate identification and assessment of sentinel lymph node (SLN) using noninvasive imaging methods can play a vital role in tumor staging, surgical planning, and prognostic evaluation. In this study, we assessed the efficacy of B7-H3-targeted molecular-ultrasound imaging for the early SLN detection, and characterization in a mouse model of orthotopic breast cancer. We established a mouse breast cancer model with lymph node metastasis by injecting MAD-MB 231 cells which were engineered to express firefly luciferase reporter gene into the fat pad of the right 4th mammary gland in female BALB/c nude mice. The sole lymph node (LN) close to the tumor was regarded as the SLN for imaging investigation, which included metastatic and non-metastatic SLNs. The LN in the right 4th mammary gland from normal mice was used as normal control (normal mice LN). The commercially available preclinical streptavidin-coated, perfluorocarbon-containing lipid-shelled microbubbles (VisualSonics, Toronto, Canada) were used to generate B7-H3-targeted microbubbles (MBB7-H3) and control microbubbles (MBControl). Then, ultrasound molecular imaging (USMI) was performed using a high-resolution transducer (MS250; center frequency, 21MHz; Vevo 2100; VisualSonics, Toronto, Canada) after intravenous injection of microbubbles. The SLN was clearly detected and located under conventional (B-mode) and contrast-enhanced ultrasonography with microbubble injection. The metastatic SLNs showed a markedly higher signal from B7-H3-targeted microbubbles (MBB7-H3) compared to the non-metastatic SLNs and normal LNs. The metastatic SLN was further confirmed by ex vivo bioluminescence imaging and eventually verified by histological analysis. Our findings suggest the potential value of USMI using B7-H3 targeted microbubbles in breast cancer and establish an effective imaging method for the non-invasive detection and characterization of SLN.

Objective To study the factors influencing the non-sentinel lymph node(NSLN) status and to assess Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram performance in predicting SLN metastases in a sentinel lymph node(SLN) positive Chinese breast cancer population. Methods Data were collected from breast cancer patients who were diagnosed with pathological positive sentinel lymph node and received further axillary lymph node dissection(ALND) in Shanghai Ruijin Hospital from January 2011 to August 2014. Use MSKCC nomogram to calculate each patient's NSLN metastasis risk score. The receiver operator characteristic curve(ROC curve)and the area under the ROC curve(AUC)was used to assess the predictive accuracy of the model. Results Among the 1147 patients who received sentinel biopsy in our center, 150 SLN positive patients who received ALND were enrolled in this study. By univariate analysis, multifocal breast cancer (P = 0.017), SLN+/SLN ratio (P = 0.010) and axillary lymphadenopathy displayed by ultrasound(P = 0.005) are the influencing factors of NSLN metastases. By multivariate analysis, multifocal breast cancer (OR 7.25, 95% CI 1.73∼30.43, P = 0.007), SLN+/SLN ratio≥0.5 (OR 2.564, 95% CI 1.22∼5.39, P = 0.013) and axillary lymphadenopathy displayed by ultrasound (OR 2.471, 95% CI 1.18∼5.19, P = 0.017) are the independent influencing factors of NSLN metastases. The AUC of MSKCC nomogram in this population is 0.677. Conclusion For breast cancer patients with positive sentinel lymph node, multifocality, SLN+/SLN ratio and axillary lymphadenopathy displayed by ultrasound is related to NSLN metastasis. MSKCC has low accuracy in predicting NSLN status of this population. Citation Format: Huang J, Chen X, Shen K, Li Y, Chen W, He J, Zhu L, Huang O, Zong Y, Fei X, Jin X. Risk factors of non-sentinel lymph node metastasis in breast cancer patients with metastatic sentinel lymph node. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-13.

Gray-Scale Contrast-Enhanced Ultrasonography Of Sentinel Lymph Nodes In A Metastatic: Breast Cancer Model

Background: Escalation of adjuvant endocrine therapy for selected hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer patients has been a standard-of-care treatment. Effective prognostic model is crucial for identifying patients who have unmet treatment needs and supporting personalized decision-making to improve the patients’ outcomes. However, existing prognostic models fallen short when applied to these patients with low recurrence risk, especially among Chinese population. Thus, we sought to develop and validate a deep learning model for HR+ early-stage recurrence prediction (HERPAI) based on conventional clinical and pathological data. Method: HR+/HER2- early-stage (T1-2N0-1) invasive breast cancer patients who received definitive surgery and followed by endocrine therapy from four independent medical centers were included in this retrospective study. Patients from center 1 were used as derivation cohort (90% in the development and 10% in the internal test cohort), while those from other centers were combined as an external test cohort. A deep learning prognostic model, HERPAI, was developed based on Transformer to predict risk of invasive disease-free survival (iDFS) utilizing clinical and pathological predictors (age, menopausal status, body mass index, family history, breast and lymph node surgery modality, T stage, N stage, histology, grade, expression levels of ER, PR, HER2, and Ki67). Hyper-parameter random searching was performed using five-fold cross-validation strategy in the development cohort. The model performance was evaluated using Concordance index (C-index) for all of the cohorts, as well as the subgroups defined by menopausal status, N stage, Ki67 expression, adjuvant chemotherapy, and radiation therapy status. Cut-off value for selecting patients with 5-year recurrence risk &amp;gt; 10% was determined in the validation cohort for risk stratification. Hazard ratio (HR) was estimated between risk groups for iDFS. The association between HERPAI score and selected gene were explored using linear regression in the patients with genetic data in the derivation cohort to provide insights into the biological foundation of HERPAI. Results: A total of 5,424 patients were included in the derivation cohort, of who 4,882 were used as development and 542 were used as internal test cohort, while 942 patients were included in the external cohort. HERPAI yielded a C-index of 0.73 (95% CI, 0.65 to 0.81) 0.73 (95% CI, 0.62 to 0.85), and 0.68 (95% CI, 0.60 to 0.77), in the validation, internal, and external test cohort, respectively. Consistent performances were observed for all pre-specified subgroups in three cohorts. High-risk patients (approximately 25% of the overall population) were associated with an increased risk of iDFS for validation (HR 2.56 [95% CI 1.25 to 5.22], P = 0.01), internal (HR 2.52 [95% CI 0.97 to 6.57], P = 0.06) and external test (HR 1.94 [95% CI, 1.00 to 3.74], P = 0.049) cohort, respectively. Moreover, HERPAI could predict distant recurrence and overall survival with a C-index of 0.68 (95% CI, 0.49 to 0.86) and 0.71 (95% CI, 0.47 to 0.94) in the external test cohort, respectively. In addition, HERPAI outperformed other prognostic factors in predicting iDFS, including T stage, N stage and Ki67 (C index ranged 0.54 to 0.59 in external test cohort). The HERPAI score was significantly associated with GRB7, GSTM1, Ki67, and RPLPO gene expression, after adjusted for age and family history (all P &amp;lt; 0.05). Conclusions: HERPAI is a promising tool for selecting vulnerable HR+/HER2- early-stage BC patients who are at high-risk of recurrence and may benefit from escalating adjuvant endocrine therapy. Citation Format: Ruixin Pan, Haoting Shi, Yiqing Shen, Xiaosong Chen, Kunwei Shen. Development and Validation of a Deep Learning Model for HR+/HER2- Early-stage Breast Cancer Recurrence Prediction (HERPAI) using Conventional Clinical and Pathological Data: A Real-world Study in Chinese Population [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-13.

To explore the feasibility of sentinel lymph node (SLN) identification by contrast-enhanced ultrasound (CEUS) in pre-operative breast cancer patients and the value of enhancement patterns for diagnosing lymph node metastases and characterising axillary nodal burden. 110 consecutive breast cancer patients were enrolled. Before the surgery, microbubbles were injected intradermally. The lymphatic drainage pathway was detected to identify the SLNs. Blue dye and indocyanine green (ICG) fluorescence were used to trace SLNs during the operation. The enhancement patterns of SLNs were recorded and compared with the final pathological diagnosis. SLN detection rate was 96.4 % of 110 patients, 134 SLNs were detected in total. The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of predicting SLNs metastases by CEUS enhancement patterns were 100 %, 52.0 %, 43.4 %, 100 % and 64.9 %, respectively. No metastatic SLNs were presented as homogeneous enhancement. Low nodal burden with 0-2 SLN metastases in 92.5 % nodes presented as heterogeneous enhancement. No enhancement pattern was proved to be SLN metastases in 100 % patients. CEUS is a feasible approach for SLN identification. CEUS enhancement patterns can be helpful in recognising metastatic SLNs and nodal burden. • CEUS is a feasible approach for SLN identification and characterisation. • The enhancement patterns on CEUS can be helpful in recognising metastasised SLNs. • Homogeneous enhancement pattern has the highest negative-predictive value.

Early metastatic progression of bladder carcinoma: molecular profile of primary tumor and sentinel lymph node.