Lymph Node Status Research Articles

Expression of CD44 in Triple Negative Breast Cancer and its Correlation with Prognostic Parameters

Background: The study aims to evaluate CD44 expression as a cancer stem cell marker in Triple-negative breast cancer (TNBC) and its correlation with prognostic parameters. Evaluation of CD44 immunoexpression in TNBC is vital for understanding tumour aggressiveness and determining its prognostic value. Methods: A hospital based cross sectional study of 50 cases of primary triple negative breast cancer patients. The tissue sections were subjected to immunohistochemical examination using CD44 antigen marker. The proportion and intensity of CD44 immunostaining was assessed and correlation with prognostic markers such as histological grade, tumor size and nodal status. Results: CD44 expression was observed in 40% of the total cases with a statistically significant association with histological grade (p-value= 0.002). Higher CD44 expression was noticed with increasing tumour grade. However, no statistical significance was observed with respect to tumour size and nodal status. Conclusion: The study suggests that CD44 immunoexpression may serve as a surrogate marker of BCSCs and may hold prognostic value in TNBC patients. However, further studies on larger samples are required to fully understand its role.

Can we skip invasive biopsy of sentinel lymph nodes? A preliminary investigation to predict sentinel lymph node status using PET/CT-based radiomics

BackgroundSentinel lymph node (SLN) biopsy (SLNB) is considered the gold standard for detecting SLN metastases in patients with invasive ductal breast cancer (IDC). However, SLNB is invasive and associated with several complications. Thus, this study aimed to evaluate the diagnostic performance of a non-invasive radiomics analysis utilizing 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) for assessing SLN metastasis in IDC patients.MethodsThis retrospective study included 132 patients with biopsy-confirmed IDC, who underwent 18F-FDG PET/CT scans prior to mastectomy or breast-conserving surgery with SLNB. Tumor resection or SLNB was conducted within one-week post-scan. Clinical data and metabolic parameters were analyzed to identify independent SLN metastasis predictors. Radiomic features were extracted from each PET volume of interest (VOI) and CT-VOI. Feature selection involved univariate and multivariate logistic regression analysis, and the least absolute shrinkage and selection operator (LASSO) method. Three models were developed to predict SLN status using the random forest (RF), decision tree (DT), and k-Nearest Neighbors (KNN) classifiers. Model performance was assessed using the area under the receiver operating characteristic curve (AUC).ResultsThe study included 91 cases (32 SLN-positive and 59 SLN-negative patients) in the training cohort and 41 cases (29 SLN-positive and 12 SLN-negative patients) in the validation cohort. Multivariate logistic regression analysis identified Ki 67 and TLG as independent predictors of SLN status. Five PET-derived features, three CT-derived features, and two clinical variables were selected for model development. The AUC values of the RF, KNN, and DT models for the training cohort were 0.887, 0.849, and 0.824, respectively, and for the validation cohort were 0.856, 0.830, and 0.819, respectively. The RF model demonstrated the highest accuracy for the preoperative prediction of SLN metastasis in IDC patients.ConclusionThe PET-CT radiomics approach may offer robust and non-invasive predictors for SLN status in IDC patients, potentially aiding in the planning of personalized treatment strategies for IDC patients.

Higher risk of recurrence in early-stage breast cancer patients with increased levels of ribosomal protein S6

PI3K/AKT/mTOR pathway is implicated in breast cancer progression and recurrence. The identification of PIK3CA and AKT1 mutations and loss of PTEN serve as selection criterion for targeted therapies involving selective inhibitors. However, they do not consistently align with pathway activation, and high-cost determinations limit their routine application. PI3K-downstream epigenetic regulatory mechanisms broaden the alterations that amplify pathway activity and, consequently, sensitivity to selective inhibitors. In this retrospective observational study, conducted within a cohort of early-stage breast cancer patients, we determined phosphorylated ribosomal protein S6 (pS6) at Ser240/244 by immunohistochemistry as an indicator of PI3K pathway activation. Log-Rank test and Cox proportional hazards regression were used to analyze the clinical relevance of pS6, alone and together with clinicopathological variables, regarding recurrence-free survival. ROC curves and the area under the curves were used to evaluate the calibration and discrimination properties of uni- and multivariate models. Our results show that a high percentage of pS6 positive tumor cells was associated with an unfavorable prognosis in a cohort of 129 hormone receptor positive/HER2 negative breast cancer patients (Hazard Ratio = 5.92; Log-Rank p = 9.5e-08; median follow-up = 53 months). When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

External beam radiotherapy followed by image-guided adaptive brachytherapy in locally advanced cervical cancer: a multicenter retrospective analysis.

To evaluate oncological outcomes and toxicities in patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy followed by image-guided adaptive brachytherapy at two Italian centres. A retrospective analysis was conducted on 122 patients with LACC treated between 2010 and 2022. Primary endpoints were local control (LC), pelvic control (PC), and nodal control (NC). Secondary endpoints included disease-free survival (DFS), metastasis-free survival (MFS), overall survival (OS), and late toxicity. Correlations between patient characteristics and oncological outcomes were conducted. Brachytherapy planning was CT and MRI-based in 88 (72.1%) and 34 patients (27.9%), respectively. The mean total dose (EQD2) delivered to high-risk clinical target volume was 82Gy. Overall treatment time was ≤ 50days and > 50days in 48 (39.3%) and 74 patients (60.7%), respectively. At a mean follow up of 101months, 3 and 5-year LC rates were 87% and 85%, respectively. Five-year PC and NC rates were 77% and 85.1%. Five-year DFS and OS were 61% and 65.4%, respectively, with significant correlations between these outcomes and FIGO stage and nodal status at diagnosis. Gastrointestinal, genitourinary and vaginal adverse effects were the most reported late toxicities and 8 (6.5%) grade 3-5 events were observed. 32 patients (26.2%) had vaginal stenosis and it was significantly related to 3D imaging used for brachytherapy planning. The study confirmed the efficacy and safety of chemoradiotherapy and IGABT for LACC. Full implementation of MRI treatment planning and interstitial techniques could further enhance personalized treatment and outcomes.

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy.

Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) haveexcluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) status (odds ratio [OR] 2.5; p < 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and twoof the three underwent ALND at the initial surgerywith no additional positive nodes. In cT1-2N0 breast cancer, HR+/HER2- status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.

Molecular Genetic Factors of Risk Stratification of Lymph Node Metastasis in Endometrial Carcinoma.

According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary.

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival

ObjectivePotential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. MethodsPatients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. ResultsSeventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), P = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), P = 0.031). ConclusionR0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).

MRI-based assessment of residual disease after neoadjuvant chemotherapy in pregnant women with cervical cancer

PurposeThis study explores the performance of MRI in detecting residual disease after platinum-based neoadjuvant chemotherapy (NACT) in pregnant cervical cancer (CC) patients, which would serve as a surrogate of treatment response. MethodsIn this retrospective single-centre study, consecutive pregnant cervical cancer patients treated with NACT and undergoing MRI examination before and at the end of the therapeutic protocol between 2010 and 2021 were included. Tumour maximum diameter and nodal status were evaluated in MRI at staging and after NACT. Patients exhibiting increased tumor burden post-NACT were excluded. On post-NACT the presence or absence of residual disease was recorded and the MRI diagnostic performance for assessing residual disease was calculated using histopathology at radical hysterectomy as the reference standard. ResultsThe study included 12 pregnant patients (median age 36 years, 27–42). At post-NACT MRI, residual disease was absent in 2/12 patients (16.7 %) while present in 10/12 (83.3 %). Histopathology was concordant in all patients without MRI residual disease and in 9/10 patients with MRI residual disease, while discordant in 1/10. MRI sensitivity, specificity, positive predictive value, negative predictive and accuracy for detecting residual disease were 100.0 % (95 %CI: 1.00, 1.00), 66.7 % (95 %CI: 0.13, 1.00), 90 % (95 %CI: 0.71, 1.00), 100 % (95 %CI: 1.00, 1.00), and 91.7 % (95 %CI: 0.76, 1.00) respectively (p = 0.045). ConclusionsThis study suggests that MRI has good diagnostic performance to detect residual disease after NACT in pregnant CC patients, and potentially assess response to treatment in this setting.

Nodal involvement in patients with small, clinically node-negative HER2-positive breast cancer after staging with FDG-PET/CT and neoadjuvant systemic therapy

BackgroundGuidelines recommend systemic therapy for stage I HER2+ breast cancer (BC). Neoadjuvant systemic treatment (NAST) allows response-guided adjuvant treatment. However, prior to NAST only clinical nodal staging is available, risking undertreatment if ypN+ is observed. Here, we aim to evaluate the impact of FDG-PET/CT and NAST on nodal disease status in patients with small, node-negative HER2+ BC. MethodsThis retrospective study included patients with small (≤3 cm), clinically node-negative HER2+ BC diagnosed between 2011 and 2023. Primary outcome was the proportion of patients with nodal disease on final pathology after upfront surgery or NAST followed by surgery with or without FDG-PET/CT. Patients received either paclitaxel + trastuzumab (PT) or a more extensive regimen. ResultsOf the 370 included patients, 183 underwent FDG-PET/CT, detecting regional or distant metastases in 14 patients (7.7 %).Among 356 patients with cN0 disease, 44.1 % (n = 157/356) had upfront surgery, with only 3 % (5/157) having an FDG-PET/CT. The remaining 55.9 % (199/356) started with NAST, with 82 % (n = 164/199) having an FDG-PET/CT. Among patients treated with NAST, 36 % received PT.Nodal involvement on pathology was seen in 19.1 % (n = 29/152) after upfront surgery without FDG-PET/CT and 6.1 % (10/164) after NAST combined with FDG-PET/CT.After NAST, 58 % had a pCR (PT: 49 %, other: 63 %). Nodal involvement on final pathology was seen in 6.9 % after PT and in 5.5 % after more extensive regimen. ConclusionsThe proportion of patients with ypN + after NAST combined with FDG-PET/CT was only 6.1 %. Neoadjuvant treatment can be a safe treatment strategy for patients with stage I HER2+ BC.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

MA08.04 Exploration on the Prognostic Heterogenicity in Stage IIB (the 9th Edition of TNM Classification) NSCLC Patients with Different Nodal Statuses

MA08.04 Exploration on the Prognostic Heterogenicity in Stage IIB (the 9th Edition of TNM Classification) NSCLC Patients with Different Nodal Statuses

The Prognostic Significance of Tumor Deposits in Non-Metastatic Colorectal Cancer: Comparing Risk of Recurrence and Metastasis with High-Risk Features

Abstract Introduction/Objective Tumor deposit (TD) is a prognostic factor in colorectal cancer (CRC) patients. This study aims to determine if TD poses a similar risk of local recurrence and distant metastasis as known high-risk (HR) features in non-metastatic CRC. Methods/Case Report An analytical cross-sectional design was employed. Our hospital clinical and pathology databases were queried for stage I-III CRC patients from January 2016 to December 2018 and divided into two groups: TD only group defined by TD on histopathology and HR group defined by obstruction, perforation, or T4- stage. The following variables were collected from each case; biological factors (age, gender, race, and BMI), tumor features (tumor size, tumor grade, presence of LVI, PNI, lymph node status and TN staging) and postoperative follow up (development of recurrence, adjuvant chemotherapy, and overall survival (OS) duration). Data were analyzed using Kruskal-Wallis test for continuous variables and chi-square and Fisher’s exact test for categorical variables. Survival analysis was conducted using Kaplan-Meier estimate graphs. Results (if a Case Study enter NA) A total of 138 non-metastatic CRC patients who underwent surgery and chemotherapy were identified. The TD group consisted of 79 (57.2%) patients with a median age of 67 y (range 35 - 94 y), including 40 (50.6%) males and 39 (49.4%) females. The HR group comprised 59 (42.7%) patients with a median age of 70 y (range 28 - 103 y), including 25 (42.4%) males and 34 (57.6%) females. There were no significant demographic differences between the groups (P&amp;gt;0.05). However, tumor size, tumor grade, presence of lymphatic vessel invasion (LVI), perineural invasion (PNI), and tumor-node (TN) staging exhibited statistically significant differences between the groups (P&amp;lt;0.05). Local tumor recurrence and/ distant metastasis occurred in 29 patients (36.7%) in the TD group and 18 patients (30.5%) in the HR group, with median time for recurrence and/or metastasis 11 months and 12 months, respectively. There was no significant difference between the groups (P&amp;gt;0.05). TD patients had a median survival duration of 42 months, whereas HR group patients had a median survival of 51 months, although this difference was not statistically significant (P&amp;gt;0.05). Conclusion In non-metastatic CRC patients, TD poses a similar risk of local tumor recurrence and distant metastasis as HR factors. HR patients may have a longer survival than TD counterpart. Based on these findings both groups should be subjected to enhanced surveillance.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor A (VEGF-A) expressions in Ethiopian female breast cancer and their association with histopathologic features.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGF) play important role in breast tumor growth, invasion, metastasis, patient survival and drug resistance. The aim of this study was to evaluate the protein expression status of EGFR and VEGF-A, as well as their association with hormone receptor status and histopathological characteristics in the invasive type of female breast cancer among Ethiopians. The primary breast tumor tissues were obtained from 85 Ethiopian invasive breast cancer cases that underwent modified radical mastectomy (MRM) from June 2014 to June 2015. Their FFPE blocks were analyzed for EGFR and VEGF protein expressions using immunohistochemical techniques. The expressions were also correlated with histopathologic features. Epidermal growth factor receptor over-expression was observed in 22% of the tumor samples. VEGF-A expression was negative in 13.41%, low in 63.41%, moderate in 20.73%, and high in 2.44%. EGFR expression, but not VEGF-A, showed a significant inverse correlation with both estrogen receptor (ER) (P = 0.01) and progesterone receptor (PR) statuses (P = 0.04). EGFR and VEGF expressions did not show significant association with tumor size, grade, lymph node status or age at diagnosis. Epidermal growth factor receptor expression was most likely associated with ER and PR negative tumors. Assessments of multiple molecular markers aid to understand the biological behavior of the disease in Ethiopian population. It might also help to predict which group of patients might get more benefit from the selected treatment strategies and which are not.

Identification Of Risk Factors Of Bone Metastasis Among Iraqi Breast Cancer Women

Background: The most common site of metastases in people with breast cancer is bone metastasis. Patients with advanced phases of cancer are associated with an increased prevalence of several types of metastases, one of which is bone metastasis. Object: Assessment of the risk factors for bone metastases in patients with breast cancer. Patients and Methods: This is a retrospective study of 316 patients with breast cancer who either had bone metastases at the time of diagnosis or developed it later on. The study was carried out between January 2013 and April 2018. Three hundred and sixteen patients were assigned into two groups. In the case group, 100 patients with breast cancer had been diagnosed with bone metastasis by CT, MRI, bone scan, and PET scan; in the control group, there were 216 cases in are control group with breast cancer metastasis to sites other than bone. The questionnaire was created to record all factors (with the exception of demographic information), such as age, histopathological reading for invasive lobular carcinoma, invasive ductal carcinoma, or another type of cancer, ER status, PR status, Her2neu status, lymph node status and stage, and menopausal status. Results: The majority were 45 years of age or younger, and 96.5% of them had invasive ductal carcinoma in terms of hormonal status. Positive ER and PR status is found in 67.7% and 67.1% of the cases, respectively; 40.5% of the cases had amplified Her2neu receptors, 78.5% of the cases had positive lymph nodes, and 41.9% of the cases had (N1) stage. The highest proportion of bone metastasis was associated with negative ER and PR receptors (46.2% and 49%, respectively), while no significant statistical association (P= 0.65). Conclusion: negative ER, PR status, and Her2neu receptors not amplified, lymph node involvement, age 45 and less, infiltrating lobular carcinoma (ILC) histological type, and menopausal state are significant risk factors for bone metastasis in breast cancer.

CD8+ T cells infiltrating into tumors were controlled by immune status of pulmonary lymph nodes and correlated with non-small cell lung cancer (NSCLC) patients’ prognosis treated with chemoimmunotherapy

PurposeNeoadjuvant chemoimmunotherapy has the potential to reduce tumor burden, improve the pathological complete response (pCR) rate, and significantly prolong patients’ disease-free survival (DFS). However, the treatment’s effectiveness varies among NSCLC patients. The immunological mechanisms contributing to tumor regression still require further exploration and elucidation. MethodsThe immune status of patients’ local tumor microenvironment (TME) before and after neoadjuvant chemoimmunotherapy, their paired pulmonary lymph nodes (11th LNs) after therapy, including infiltrating immune cell densities and their correlations, were analyzed using multiplex immunofluorescence. ResultsFifty-six NSCLC patients undergoing neoadjuvant chemoimmunotherapy were enrolled and subsequently underwent surgical resection and pathological evaluation. Among these, 19 patients achieved a pCR, 6 patients exhibited a major pathological response (MPR), and 31 patients did not achieve MPR. There were no significant difference in the densities of CD8+ T cell, Treg and Dendritic cell (DC) in patients’ TME before neoadjuvant therapy (n = 26, P = 0.091, P = 0.753, P = 0.905, respectively), but after treament, these immune cells’ dynamics were significantly different between different response group. CD8+ T cell densities were increased in pCR gourp (P = 0.006), but not in non-pCR group (P = 0.389); the densities of Treg were increased in non-pCR gourp (P = 0.0004), but DC were significantly decreased in non-pCR gourp (P = 0.005). After surgery, the TME were also significantly different: patients achieving pCR typically demonstrated high densities of CD8+ T cell, DC and low densities of Tregs (P = 0.0001, P < 0.0001 and P = 0.0004). The immune status of 11th LNs also exhibited significant differences. DC densities were much higher in pCR patients, whereas Treg in the pCR group were significantly lower than those in the non-pCR group (P = 0.0008 and P = 0.003). Furthermore, the densities of DC in the TME showed a moderate positive correlation with DC in 11th LNs (P = 0.0002), while the densities of Tregs in the TME exhibited a moderate negative correlation with DC densities in 11th LNs (P = 0.03). Patients who had high densities of CD8+ T cell in the resection tissues and DC in the LNs, experienced longer DFS (P = 0.048 and P = 0.024). ConclusionImmune cells in both pulmonary LNs and the TME collectively influence the remodeling of the NSCLC patient’s TME, thus impacting treatment response and prognosis.

The Utility of PRAME and Ki-67 as Prognostic Markers for Cutaneous Melanoma.

Cutaneous melanoma can lead to metastasis, and it is associated with high mortality. Currently, there are no widely accepted immunohistochemistry markers for melanoma prognosis in routine staging. Preferentially expressed antigen in melanoma (PRAME) is a possible biomarker for prognosis in several noncutaneous neoplasms. Ki-67 is a cell proliferation marker correlated with poor outcomes in many cancers. This study assessed PRAME and Ki-67 as potential prognostic markers for sentinel lymph node outcomes and survival among melanoma patients. This is a retrospective study analyzing cutaneous melanoma cases from a Brazilian cancer center (2005-2021). All cases were tested using immunohistochemistry to evaluate PRAME expression and Ki-67 index. Descriptive analysis, Spearman correlations, means comparison, Kaplan-Meier analysis, χ2, and Cox models were performed. In univariate analysis of 123 cutaneous melanoma cases, high extent (P = 0.0267) and elevated intensity (P = 0.043) of PRAME were associated with decreased overall survival. The Ki-67 index was associated with overall survival (P = 0.05) and sentinel lymph node status (P = 0.0403), with a positive correlation between the markers (P = 0.0004) and between Ki-67 and Breslow thickness (P = 0.0001). However, in multivariate analysis, only Breslow thickness significantly influenced overall survival (P = 0.0003). Then, the present results can suggest that elevated PRAME and Ki-67 expression are associated with poor overall survival in cutaneous melanoma; however, in multivariate analysis, only the Breslow thickness had a significant influence. These findings highlight the potential of PRAME and Ki-67 as prognostic markers, opening frontiers that could improve strategies for treating cutaneous melanoma.

Real-World Implications of the SOUND Trial.

The SOUND trial demonstrated that omission of sentinel lymph node biopsy (SLNB) is noninferior to axillary staging in patients with early-stage breast cancer (BC) and negative axillary ultrasound (AxUS). We examined the generalizability of these findings in patients with hormone receptor (HR)+HER2- disease. Patients with cT1N0M0, HR+HER2- BC and negative AxUS undergoing breast conservation with SLNB from 2016 to 2023 were identified from a prospectively maintained database. Clinicopathologic characteristics, disease burden, adjuvant treatment, and oncologic outcomes were examined and compared with the SLNB arm of the SOUND trial. In postmenopausal patients, the impact of nodal status and 21-gene recurrence score on chemotherapy recommendations were also examined. Of 3972 patients with cT1N0M0 HR+HER2- breast cancer, 544 underwent AxUS; 312 met SOUND eligibility criteria. Median age was 57 (interquartile range [IQR] 48-64) years, and 199 (63.8%) were postmenopausal. Median (IQR) tumor size was 1.3 (0.9-1.7) cm, and 260 (83.3%) tumors were grade 1 or 2. Sentinel lymph node biopsy was positive in 38 (12.2%) patients. Only three (0.4%) had ≥ 4 positive lymph nodes. At a median follow-up of 26.2 (IQR 10.8-38.2) months, there were no axillary recurrences and one (0.3%) distant recurrence. Among postmenopausal women with recurrence score ≤ 25, chemotherapy recommendations were not associated with nodal status. Examination of our real-world HR+ HER2- "SOUND-eligible" population suggests that nodal disease burden and oncologic outcomes are similar to the SOUND trial population, supporting careful implementation of trial results into multidisciplinary practice. In postmenopausal patients, omission of SLNB does not appear to impact adjuvant chemotherapy recommendations.

Lateral node metastasis in low rectal cancer as a hallmark to predict recurrence patterns.

Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.