Node Micrometastases Research Articles

Prognostic value of isolated tumor cells and micrometastasis of lymph nodes in invasive urinary bladder cancer.

The prognostic significance of nodal micrometastasis and isolated tumor cells (ITC) in urinary bladder cancer (UBC) is unknown. We aimed to evaluate the prevalence, clinical impact, and clinicopathological characteristics of nodal micrometastasis and ITC in UBC. A total of 124 patients with UBC undergoing surgery were investigated. Detection of micrometastasis and ITC was performed using pancytokeratin immunohistochemistry (IHC). Histopathologic and clinical findings were correlated with patients' outcome. IHC detected nodal micrometastasis and ITC (pNmi group) in 12.9% (13/101) of originally node-negative patients and in 26.1% (6/23) of originally node-positive patients (pN+ group). The remaining 88 were truly node-negative patients (pN0 group). After IHC, all 13 patients in the pNmi group were upstaged from pN0 to pN1-2 and one patient in the pN+ group was changed from pN1 to pN2. Nodal micrometastasis and ITC were significantly associated with mixed urothelial carcinoma (UC) (p = 0.002), UC with discohesive pattern (p = 0.006), glandular differentiation (p = 0.043), lymphovascular invasion (p = 0.009), and budding-like tumor cell clusters (p = 0.002). The pNmi group had significantly worse cancer-specific survival than the pN0 group in univariate (p = 0.004) and multivariate (p = 0.040) analysis. IHC frequently identified nodal micrometastasis and ITC in originally node-negative UBC patients on routine pathological examination. Nodal micrometastasis and ITC were independently associated with cancer-related mortality in UBC. IHC might be selectively used to detect micrometastasis and ITC in UBC having specific pathological features.

Short- and long-term immunosuppressive effects of melanoma influence the prognostic value of the sentinel lymph node status

BackgroundPresence of micrometastases in the sentinel lymph node (SLN) is currently used to assess prognosis of melanoma patients. The immunoactivity within the SLN is known to be influenced by the primary tumor (PT), which may in turn impact the SLNs’ metastatic state. AimWe characterize the temporal dependence and underlying mechanisms of the immunological effects of the PT on the SLN. MethodsThe prognostic value of SLN state as a function of PT removal time was evaluated. To put the results into a functional context, selected PTs and corresponding SLNs were analyzed for gene and protein expression patterns. ResultsIn a cohort of 202 patients with known distant metastasis and similar PT prognostic characteristics, SLNs removed before or within one week after the PT (IM-SLN) had a higher incidence of micrometastases than those removed at least one week after the PT (DEL-SLN).The immunoactivity in IM-SLN was found to be lower than in DEL-SLN. Specifically, in IM-SLNs, T helper 17 / regulatory T-cells were predominant, whereas in DEL-SLNs, cytotoxic γδT-cells were more frequent. The higher immune activity in DEL-SLNs was probably facilitated by CD209+ antigen-presenting cells. Indeed, in PT with high TGFβ expression CD209+ cells appear to be trapped and no increased immunoactivity was observed in DEL-SLN. ConclusionsPresence of micrometastases in DEL-SLNs have a higher negative prognostic value as in IM-SLNs since they indicate not only a melanoma’s propensity to metastasize, but possibly also its capacity to escape immune responses.

Impact of molecular classification on recurrence risk in endometrial cancer patients with lymph node metastasis: multicenter retrospective study

ObjectiveTo assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery.MethodsEndometrial cancer...

Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy

IntroductionThe significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST.MethodsThis retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model.ResultsOf the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42–2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12–4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%).ConclusionsSLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma insitu with microinvasion.

To address the question of axillary lymph node staging in ductal carcinoma insitu with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Abstract PO3-17-05: Clinical Characteristics and Outcomes of Patients Receiving Adjuvant Paclitaxel and Trastuzumab (APT regimen) for HER2-Positive Early-Stage Breast Cancer in Brazil: A Real-World Evidence

Abstract Introduction: The APT trial established adjuvant paclitaxel and trastuzumab (TH) as the standard of care for HER2-positive early-stage breast cancer with tumor size ≤ 3 cm and no more than one lymph-node micrometastasis. This single-arm phase II trial demonstrated favorable long-term outcomes, with a 3-year invasive disease-free survival (IDFS) rate of 98.7% (95% CI 97.6 – 99.8%). In an updated follow-up analysis, the 10-year IDFS and overall survival (OS) rates were 91.3% (95% CI 88.3 – 94.4%) and 94.3% (95% CI 91.8 – 98.3%), respectively. Nevertheless, outcomes observed in real-world scenarios have frequently been less favorable than those observed in clinical trials. We aimed to characterize the population receiving the APT regimen in clinical practice and evaluate if real-world outcomes align with those observed in the pivotal clinical trial. Methods: This retrospective cohort study included patients with HER2-positive early-stage breast cancer treated between 2015 and 2023 at four Brazilian cancer institutions, including public and private hospitals. Clinical and demographic data, treatment details, and outcomes were collected from electronic records. The primary endpoints were the 3-year and 7-year invasive disease-free survival (IDFS) rates. Secondary endpoints included overall survival (OS) and factors associated with IDFS. Survival analysis employed the Kaplan-Meier method, and Cox regression assessed prognostic factors. Results: A total of 133 patients treated with the APT regimen were evaluated, with a median age of 56 years (range 20–83). The majority had no special type breast carcinoma (92.4%), grade 2 (63.4%) or grade 3 (34.3%) tumors, no angiolymphatic invasion (76.3%), positive estrogen receptor (69.9%), positive progesterone receptor (55.6%), and node-negative disease (94.7%). Tumor staging distribution was as follows: T1a (12%), T1b (23.3%), T1c (49.6%), and T2 (13.5%). Most patients (95.4%) received the APT regimen as per guideline recommendations, while 3.8% received it due to contraindication to other therapies. With a median follow-up of 45.8 months, 8 patients (5.8%) experienced an invasive disease event or death from any cause: 5 (3.8%) had distant recurrence, 1 (0.8%) had local recurrence, and 2 (1.5%) died without recurrence. Notably, these events occurred in patients receiving the APT regimen according to standard indications, except for one patient with N+ disease and a contraindication to another regimen. The recurrence rate according to the T stage is presented in the Table. The 3-year IDFS rate was 100% (95% CI not applicable). All events occurred after the 3-year time point, resulting in a 7-year DFS rate of 80.8% (95% CI 62.7–90.7%). No prognostic factors related to IDFS were identified. Four patients died during the study period, yielding a 7-year OS rate of 88.0% (95% CI 61.6–96.6%). Conclusion: While the baseline characteristics of this cohort resembled those of the APT trial, the long-term outcomes observed in the real-world setting were less favorable. Further investigation is required to determine the reasons for this discrepancy, underscoring the necessity for larger real-world data studies to validate these findings. Recurrence rate according to T stage XX XX Citation Format: Giselle Carvalho, Renata Colombo Bonadio, Pedro Bergmann, Marina Nishimuni, André Rossi, Cristiano Souza, Gabriel Guimarães, Laura Testa, José Bines. Clinical Characteristics and Outcomes of Patients Receiving Adjuvant Paclitaxel and Trastuzumab (APT regimen) for HER2-Positive Early-Stage Breast Cancer in Brazil: A Real-World Evidence [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 PO3-17-05.

Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.

Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year. This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up. Thisis a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples. Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes.This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients. Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.

Prognostic role of lymph node micrometastasis in pN0 esophageal cancer: A meta-analysis.

To further identify the association between the lymph node micrometastasis (LNM) and long-term survival among pN0 esophageal cancer patients receiving the surgery. Several databases were searched for relevant studies up to June 22, 2023. The primary and secondary outcomes were separately overall survival (OS) and relapse-free survival (RFS) and hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Subgroup analysis based on pathological type and source of HR was further performed. All statistical analyses were conducted by STATA 15.0 software. A total of 20 studies involving 1830 pN0 patients were included in this meta-analysis. The pooled results demonstrated that the presence of LNM indicated significantly worse OS (HR = 2.19, 95% CI = 1.77-2.70, P < .001) and RFS (HR = 2.15, 95% CI = 1.65-2.80, P < .001). Besides, subgroup analysis for the OS and RFS stratified by the pathological type (squamous cell carcinoma vs mixed esophageal cancer) and source of HR (reported vs estimated) further identified the significant relationship of LNM with prognosis in surgical esophageal cancer. The presence of LNM indicated significantly poorer long-term survival among operated pN0 esophageal cancer patients. LNM could serve as a novel and reliable prognostic indicator in surgical esophageal cancer.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study

The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P=0.023; 0.879 [0.767-0.950], P=0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P>0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P=0.041) to the level of senior pathologists (both P>0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P<0.0001;-34%, P<0.0001;-29%, P<0.0001; and-27%, P=0.00031). ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Abstract 3466: Prognostic implications of lymph node micrometastasis in patients with gastric cancer

Abstract Purpose: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of patients with LNMM GC.Methods: A total of 624 patients with pathologically lymph node metastasis negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Results: Patients with lymph node tumors of diameter &amp;lt; 1500 μm (LNMM) had significantly better prognosis than those with tumors of diameter ≥ 1500 μm (p = 0.012; log-rank test). Cox’s proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for overall survival of patients with pN1 GC. There was no significant difference in overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). Conclusions: LNMM is associated with favorable prognosis and could be an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered as one of the factors preventing adjuvant chemotherapy. Citation Format: Atsushi Yamamoto, Hirotaka Okamoto. Prognostic implications of lymph node micrometastasis in patients with gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3466.

128 (PB-128) Poster - Impact of Oncotype DX Recurrence Score and Nottingham Prognostic Index on adjuvant treatment in patients with axillary lymph node micrometastasis in early breast cancer

128 (PB-128) Poster - Impact of Oncotype DX Recurrence Score and Nottingham Prognostic Index on adjuvant treatment in patients with axillary lymph node micrometastasis in early breast cancer

NUF2 Expression in Cancer Tissues and Lymph Nodes Suggests Post-Surgery Recurrence of Non-Small Cell Lung Cancer.

In non-small cell lung cancer (NSCLC) cases, detecting potential lymph node metastases is essential to determine the indications for sublobar resection or adjuvant therapy. NUF2 is a tumor-specific antigen that is highly expressed in lung cancer tissues. However, the significance of analyzing NUF2 expression in dissected lymph nodes has not yet been studied. Thus, we investigated the association between NUF2 expression in lung cancer tissues and dissected lymph nodes and early recurrence of NSCLC to determine its usefulness as a marker of lymph node micrometastasis. This retrospective study quantified NUF2 expression in the cancer tissues of 88 patients with NSCLC who underwent complete resection using real-time polymerase chain reaction and investigated its relationship with clinicopathological features and prognosis. We also quantified NUF2 RNA expression in mediastinal lymph nodes from 255 patients with pN0 NSCLC who underwent complete resection with lymph node dissection and analyzed its association with prognosis. NUF2 expression in primary tumors was correlated with lymph node metastasis and unfavorable outcomes in terms of poor recurrence-free and cancer-specific survival. In N0 NSCLC cases, high NUF2 expression in mediastinal lymph nodes indicated poor prognosis, especially in lymph node recurrence. NUF2 emerges as a promising marker for predicting lymph node metastatic recurrence, offering potential utility in guiding post-surgical adjuvant therapy for lung cancer or assisting in intraoperative decisions for sublobar resection.

Frequency and predictive factors of nodal micro-metastasis (NMM) in resectable non-small cell lung cancer.

The frequency of lymph nodal micrometastasis (NMM) in resectable non-small cell lung cancer (NSCLC) is frequently underestimated when relying solely on standard hematoxylin and eosin staining during pathological examination. This is a retrospective cross-sectional diagnostic research. Medical records of resectable pN0 NSCLC patients who underwent curative resection in Maharaj Nakorn Chiang Mai Hospital between January 2006 to December 2017 were retrospectively reviewed. Immunohistochemistry (IHC) staining using cytokeratin AE1/AE3, p53 and BerEP4 markers was employed to detect NMM. Primary objective of this study was to determine frequency of NMM in pN0 resectable NSCLC. This study included 98 patients with pN0 NSCLC, of which 47 were male and 51 were female. NMM was detected in 21 of 98 patients (21.43%). Lymph node station 10 and 7 were the most common site of micrometastasis among patients with N1 and N2 micrometastasis, respectively. Cytokeratin AE1/AE3 was the most sensitive antibody in detecting micrometastasis in lymph nodes, identifying 25 out of 27 positive lymph nodes. Tumor size greater than 4 cm was a statistically significant predictive factor for NMM with risk ratio 6.69 [95% confidence interval (CI): 2.38-18.85, P<0.001]. NMM was identified in 21.43% of pN0 resectable NSCLC patients and tumor size greater than 4 cm is predictive factor for NMM.

Cross-attention-based saliency inference for predicting cancer metastasis on whole slide images.

Although multiple instance learning (MIL) methods are widely used for automatic tumor detection on whole slide images (WSI), they suffer from the extreme class imbalance WSIs containing small tumors where the tumor may include only a few isolated cells. For early detection, it is important that MIL algorithms can identify small tumors. Existing studies have attempted to address this issue using attention-based architectures and instance selection-based methodologies but have not produced significant improvements. This paper proposes crossattention-based salient instance inference MIL (CASiiMIL), which involves a novel saliency-informed attention mechanism to identify small tumors (e.g., breast cancer lymph node micro-metastasis) on WSIs without needing any annotations. In addition to this new attention mechanism, we introduce a negative representation learning algorithm to facilitate the learning of saliencyinformed attention weights for improved sensitivity on tumor WSIs. The proposed model outperforms the state-ofthe-art MIL methods on two popular tumor metastasis detection datasets. The proposed approach demonstrates great cross-center generalizability, high accuracy in classifying WSIs with small tumor lesions, and excellent interpretability attributed to the saliency-informed attention weights. We expect that the proposed method will pave the way for training algorithms for early tumor detection on large datasets where acquiring fine-grained annotations is is not practical.

Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

Breast cancer subtypes, distinguished by hormone receptor (HR) and HER2 status, have different clinicopathologic features. With recognition of the clinical relevance of HER2-low, there is debate as to whether this is a distinct subtype. Our study aimed to determine whether HER2-low breast cancers have specific clinicopathologic features that differ from those of HER2-negative and HER2-positive cancers. A total of 11,072 patients undergoing upfront surgery from 1998 to 2010 were identified from a single-institution prospectively maintained database. HER2 status was classified by immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) as HER2 negative (41.2%), HER2 low (45%; IHC 1+ or 2+ with negative FISH), and HER2 positive (13.7%), and stratified by HR status. Univariate (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Compared with HER2-negative tumors, HER2 low was associated with lymphovascular invasion [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.06-1.36; p = 0.003], multifocality (OR 1.26, 95% CI 1.12-1.42; p < 0.001), nodal micrometastasis (OR 1.15, 95% CI 1.02-1.31; p = 0.024), and lower rates of ≥ 3 positive nodes (OR 0.77, 95% CI 0.66-0.90, p = 0.001). When stratified by HR expression, in both HR-positive and HR-negative tumors, age and multifocality were associated with HER2 low on UVA. On MVA, no variables were independently associated with both HR-negative and HR-positive/HER2-low tumors compared with HER2-negative tumors. In contrast, HER2-positive tumors, regardless of HR status, were associated with multifocality and an extensive intraductal component. Clinicopathologic features of HER2-low tumors appear to be primarily related to HR status. Our findings do not support the characterization of HER2 low as a separate subtype.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Dual-radionuclide in vivo imaging of micro-metastasis and lymph tract with submillimetre resolution

Multi-radionuclide in vivo imaging with submillimetre resolution can be a potent tool for biomedical research. While high-resolution radionuclide imaging faces challenges in sensitivity, multi-radionuclide imaging encounters difficulty due to radiation contamination, stemming from crosstalk between radionuclides and Compton scattering. Addressing these challenges simultaneously is imperative for multi-radionuclide high-resolution imaging. To tackle this, we developed a high-spatial-resolution and high-energy-resolution small animal single-photon emission computed tomography (SPECT) scanner, named CdTe-DSD SPECT-I. We first assessed the feasibility of multi-tracer SPECT imaging of submillimetre targets. Using the CdTe-DSD SPECT-I, we performed SPECT imaging of submillimetre zeolite spheres absorbed with 125I- and subsequently imaged 125I-accumulated spheroids of 200–400 µm in size within an hour, achieving clear and quantitative images. Furthermore, dual-radionuclide phantom imaging revealed a distinct image of the submillimetre sphere absorbed with 125I- immersed in a 99mTc-pertechnetate solution, and provided a fair quantification of each radionuclide. Lastly, in vivo imaging was conducted on a cancer-bearing mouse with lymph node micro-metastasis using dual-tracers. The results displayed dual-tracer images of lymph tract by 99mTc-phytic acid and the submillimetre metastatic lesion by 125I-, shown to align with the immunofluorescence image.

Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) - a survival analysis from a prospective observational study

Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) - a survival analysis from a prospective observational study

729P Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study

729P Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model

Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.