Lymph Node Involvement In Patients Research Articles

Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi Institutional Study.

This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

Prognostic Significance of the Highest Mediastinal Lymph Node Involvement in Patients with Stage III-N2 Non-small Cell Lung Cancer.

Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial. A total of 486 patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups-HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan-Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS). The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%; p<0.001) and stage IIIA (87.2% vs. 77.5%; p<0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%, p<0.001; OS: 42.1% vs. 59.2%, p=0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio [aHR] 1.26, 95% confidence interval CI 0.94-1.68; OS: aHR 1.45, 95% CI 1.07-1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06-2.02; OS: aHR 1.70, 95% CI 1.19-2.42); however, no such difference was observed within the stage IIIB group. HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.

Determination of the Ki-67 threshold value for predicting lymph nodes involvement in patients with gastric cancer

The search for biological markers to assess metastatic involvement of the lymph nodes in gastric cancer is one of the key steps in determining treatment tactics. The role of Ki-67 as a marker of cell proliferation in gastric cancer remains relevant. The aim of our study is to determine the Ki-67 threshold value for predicting the lymph nodes metastases. A retrospective analysis of 154 patients with gastric cancer showed an independent and statistically significant relationship between the depth of tumor invasion T (p = 0.002), the differentiation grade G (p = 0.010), the value of the Ki-67 index (p &lt; 0.0001) and metastatic involvement of the lymph nodes. Using ROC analysis we found that Ki-67 ≥ 45 % correlates with the optimal level of sensitivity (55.9 %), specificity (84.2 %) and accuracy (73.4 %) of the method AUC 0.738 (p &gt;&lt; 0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients&gt;&lt; 0.0001) and metastatic involvement of the lymph nodes. Using ROC analysis we found that Ki-67 ≥ 45 % correlates with the optimal level of sensitivity (55.9 %), specificity (84.2 %) and accuracy (73.4 %) of the method AUC 0.738 (p &lt; &lt; 0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients &gt;0.043; 95 % CI 0,654–0,823). When evaluating the overall survival of patients with Ki-67 &gt; 45 %, we found that the median OS was 32 months [HR 2.2; 95 % CI 1.2–3,9; p = 0.005], while it was not reached in the group with Ki-67 &lt; 45 %.A Ki-67 level of ≥ 45 % is the optimal threshold for determining the likelihood of lymph node metastasis in gastric cancer.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer

ImportanceThe identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in breast cancer patients. The current study aims to investigate if tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. MethodsWe included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases (AXN+) as well as 230 patients without lymph node metastasis. Based on pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DE-MRI), we assessed contact of the tumor to the internal mammary perforating vessels (IMPV). Results59 patients had ipsilateral IMN+ (iIMN+), 10 patients contralateral IMN+ (cIMN+) and 228 patients had ipsilateral axillary metastases without IMN. 230 patients had node negative breast cancer. In patients with ipsilateral IMN+, 100% of tumors had contact with ipsilateral IMPV with 94.9% (n=56) classified as major contact. In iIMN- patients on the other hand, major IMPV contact was observed in only 25.3% (n=116) and 36.2% (n=166) had no IMPV contact at all. Receiver operating characteristic (ROC) analysis revealed that “major IMPV contact” was more accurate in predicting ipsilateral IMN+ (AUC 0.85) compared to a multivariate model combining grade of differentiation, tumor site, size and molecular subtype (AUC 0.65). Strikingly, among patients with contralateral IMN+ (cIMN+), 100% of tumors had contact to a crossing contralateral IMPV, whereas in contralateral IMN- (cIMN-) patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. ConclusionTumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of breast cancer patients for IMNI.

Oncologic safety of autologous fat grafting in primary breast reconstruction after mastectomy for cancer

IntroductionAutologous fat transfer (AFT) is widely used to improve results of breast reconstructive surgery, but its safety is controversial. Our objective was to evaluate the oncologic safety of AFT in a homogeneous population of patients who underwent a total mastectomy with immediate reconstruction for breast cancer. MethodsWe performed a retrospective cohort study by identifying all patients who underwent immediate breast reconstruction after mastectomy for breast cancer from 2007 to 2015 in our center. A patient group with AFT performed in the 24 months after mastectomy was compared to a control group. ResultsFive hundred fifty cases were included, of whom 136 (24.7%) underwent at least one fat graft transfer. Median age was 51 years. Reconstruction was performed in 465 (84.5%) with an implant reconstruction. The median time from mastectomy to AFT was 13.8 months. The median follow up was 55.2 months. A total of 53 events were observed, including 10 (7.4%) in the AFT group and 43 (10.4%) in the control group. There was no difference in 5-year recurrence-free survival (RFS) between the groups. In the subgroup analysis, only lymph node involvement in patients who underwent AFT in the first 24 months after oncologic surgery appeared as a risk factor of recurrence. Among the 104 patients with lymph node involvement, 5-year RFS was 69.2% in patients with lipofilling vs 92.5% in patients without it (p = 0 0.0351). ConclusionPerforming early lipofilling in primary breast reconstruction after mastectomy for cancer seems to be oncologically safe. Lymph node involvement increases the risk of recurrence in this population.

Bulky nodal disease as distinctive prognosticator in anal cancer management.

1 Background: This study aimed to investigate the prognostic value of bulky nodal involvement in patients with squamous cell carcinoma of anus treated with definitive chemoradiotherapy. Methods: Medical records of patients with anal squamous cell carcinoma receiving definitive chemoradiotherapy at three medical centers from 2004 to 2021 were retrospectively analyzed. Exclusion criteria were (1) distant metastasis including non-regional nodal involvement at diagnosis, (2) 2D radiotherapy, and (3) salvage treatment for local relapse. Bulky nodal disease was defined as node with long-diameter 2cm or greater. Results: A total of 104 patients were accrued, consisting of 51 patients without, 46 patients with non-bulky, and 7 patients with bulky nodal involvement. Median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated progression-free survival (PFS), loco-regional recurrence free survival (LRRFS) and overall survival (OS) at 5 years for patients with bulky nodal disease were 42.9%, 42.9%, and 89.4%, respectively. Compared to without or with non-bulky nodal involvement, bulky nodal involvement was significantly related with poor PFS and LR RFS. New staging incorporating bulky nodal disease as N2 stage was devised: T1-2N0-1 as stage I, T3-4N0-1 as stage II, and N2 as stage III. Estimated PFS, LRRFS, and OS at 5 years were as follows: 83.5%, 85.9%, and 91.3%, 60.9%, 67.7% and 93.3%, and 42.9%, 42.9%, and 55.6% for patients with stage I, II, and III disease, respectively (p = 0.0024 for PFS, 0.0015 for LRRFS, and 0.28 for OS, respectively). Conclusions: Patients with bulky nodal disease receiving standard chemoradiotherapy had poor survival outcomes compared to the other patient groups, suggesting the need for further treatment intensification. Moreover, incorporating bulky nodal disease into the staging system improved the prognosis predictability.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study

ContextDespite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. Evidence SynthesisWe retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. Evidence AcquisitionWe included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). ConclusionsPSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Clinical importance of serum and pleural fluid prominin-1 and hypoxia-inducible factor-1α concentration in the evaluation of lymph node involvement in patients with malignant pleural effusion.

Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was to determine whether hypoxia-inducible factor-1α (HIF-1α) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE. Fifty-six patients with MPE and 30 healthy control subjects were included. Computerized tomography (CT) and positron emission tomography (PET) were used to diagnose pleural effusion. Patients with malignant cells in pleural fluid cytological examination were included in the MPE group. Thirty-five patients with lymph node metastases on CT were included in the LNM-positive MPE group. Serum and pleural fluid HIF-1α and CD-133 concentrations were measured manually via enzyme-linked immunosorbent assay (ELISA). Serum concentrations of HIF-1α and CD133 were higher in MPE patients. It was found that CD133/HIF-1α (S) ratio was higher in the malignant patient group with positive lymph node involvement than in the negative group, while concentrations of HIF-1α (P) were lower. Pleural fluid HIF-1α and CD133/HIF-1α (S) ratio had sufficient performance in diagnosing lymphatic metastases in patients with MPE (AUC = 0.90 and 0.83, respectively). In conclusion, serum HIF-1α and CD133 concentrations were higher in patients with MPE, consistent with our hypothesis. Concentrations of HIF-1α (P) and CD133/HIF-1α (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment.

Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma

BackgroundAxillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma. Objectivesour study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma. MethodsThis is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Center of Tours between January 1, 2007 and December 31, 2018.The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659. ResultsOur study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94 % for N0 patients, 92.4 % for low-risk patients, 85.6 % for intermediate-risk patients and 58.5 % for high-risk patients. The 5-year distant metastasis-free survival was 98.2 % for N0 patients, 95.9 % for low-risk patients, 80.1 % for intermediate-risk patients, and 60.3 % for high-risk patients.Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors. However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival. ConclusionOur study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.

Demographic Factors Predict Risk of Lymph Node Involvement in Patients with Endometrial Adenocarcinoma.

The presence of lymph node positivity (LN+) guides adjuvant treatment for endometrial adenocarcinoma (EAC) patients, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Sociodemographic factors in addition to pathologic tumor characteristics may more accurately predict risk of LN+ in EAC patients. Patients diagnosed between 2004 and 2016 with pathologic T1-T2 EAC who had at least one lymph node sampled at the time of surgery in the National Cancer Data Base were included. Pathologic primary tumor predictors of LN+ were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN+, nomograms were generated. Among the 35,170 EAC patients included, 2864 were node positive. Using multivariable analysis, younger patient age (OR 0.98, 95% CI 0.98-0.99, p < 0.001), black versus white race (OR 1.19, 95% CI 1.01-1.40, p = 0.04), increasing pathologic tumor stage and grade, increase in tumor size, and presence of lymphovascular invasion were predictive of regional LN+. Both black versus white (OR 1.64, 95% CI 1.27-2.09, p < 0.001) and other versus white race (OR 1.54, 95% CI 1.12-2.07, p = 0.006) strongly predicted paraaortic LN+ in the multivariable analysis. Independent subset analyses of black and white women revealed that tumor grade was a stronger predictor of LN+ among black women. In addition to standard pathologic tumor features, patient age and race were associated with a higher risk of regional LN+ generally and paraaortic LN+ specifically. This information may inform adjuvant treatment decisions and guide future studies.

Neoadjuvant Therapy and Axillary Lymph Node Status in HER2-Positive Breast Cancer

Based on an estimating model, the aim of our study was to evaluate the axillary lymph node involvement of patients with primary invasive early human epidermal growth factor receptor 2 (HER2)-positive breast cancer before receiving neoadjuvant therapy (NAT). Patients with primary surgery (n = 63) were compared with patients who had received NAT (combined chemo/HER2-targeted antibody therapy) before surgery (n = 152). In patients receiving NAT, a positive N stage was estimated in 73.2 (49.8%) tumors resulting in a conversion (positive N stage-ypNpositive) of 35.5%. In 126 cases with ypN0 stage, a positive N stage was estimated in 41.4%.

The Evaluation of Sentinel Lymph Node Biopsy Using Radiocolloid in First Stage Endometrial Cancer.

Detection of a sentinel lymph node (SLN) in patients with endometrial cancer (EC) reduces the rate of unnecessary systemic lymph dissection. The aim of this study was to assess the SLN detection rate, accuracy of the method using Tc-99m-SENTI-SCINT and the rate of metastatic nodal involvement in patients with preoperative first stage EC. A prospective study of SLN biopsy of 41 patients with stage I EC was conducted after cervical application of 4mCi Tc-99m-SENTI-SCINT. Planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) of the pelvis were performed, followed by site-specific lymphadenectomy in intermediate-risk patients if no SLN was detected per hemipelvis and pelvic lymphadenectomy in all high-risk patients. Pre-operative detection rate of planar lymphoscintigraphy was 80.49 [95% confidence interval (CI): 68.36-92.62] and of SPECT/CT 95.12 (95% CI: 88.52-101.7). The total intraoperative SLN detection rate was 95.12 (95% CI: 88.52-101.7) per patient and 26.83 (95% CI: 19.91-33.75) bilaterally. The average number of SLNs removed was 1.6±0.8. The most common anatomical location of SLN was the right external iliac region. The SLN metastatic rate was 17%. Both sensitivity and negative predictive value regarding metastatic involvement were 100%. The SLN detection rate, sensitivity and negative predictive value using Tc-99m-SENTI-SCINT in patients with EC in our study were high. The application of ultra-staging in the histopathological analysis of SLN increases the detection of nodal metastases and improves the staging in these patients.

IL-33-expressing microvascular endothelial cells in human esophageal squamous cell carcinoma: Implications for pathological features and prognosis.

Accumulating evidence suggests that interleukin (IL)-33 plays a critical role in regulating angiogenesis and cancer progression. In this study, we characterized the pathological importance of IL-33 deployed by tumor microvascular endothelial cells (ECs) in human esophageal squamous cell carcinoma (ESCC). The expression of IL-33 in microvascular ECs in 80 cases of ESCC was examined with immunohistochemistry (IHC) and double immunofluorescence. IHC results showed that strong IL-33-immunoreactivity (IR) in microvessels, which were confirmed to be ECs by double immunofluorescence staining with IL-33/CD31 antibodies. Moreover, high proliferative activity was shown in IL-33-positive ECs, and the IL-33 functional receptor ST2 was expressed in microvascular ECs. Clinicopathological analysis revealed that IL-33-positive microvessel density (MVD) was positively correlated with node involvement in patients with ESCC. A log rank test showed a highly significant inverse correlation between the densities of IL-33-positive MVDs and overall survival rate, and patients with higher IL-33-positive MVDs tended to have a lower survival rate (both p<0.05). Therefore, we concluded that IL-33 deployed by microvascular ECs correlates with advanced pathological features and the long-term survival rate, which provides new insights into the regulatory mechanisms of tumor angiogenesis in the tumor microenvironment and might serve as a promising target in patients with ESCC.

Diagnostic Accuracy of Magnetic Resonance Imaging in the Pre-Operative Staging of Cervical Cancer Patients Who Underwent Neoadjuvant Treatment: A Clinical-Surgical-Pathologic Comparison.

Magnetic resonance imaging (MRI) has been proven to ensure high diagnostic accuracy in the identification of vaginal, parametrial, and lymph node involvement in patients affected by cervical cancer (CC), thus playing a crucial role in the preoperative staging of the disease. This study aims to compare the accuracy of MRI for the preoperative staging of patients with CC who underwent neoadjuvant treatment (NAT) or direct surgery. Retrospective data analysis of 126 patients with primary CC International Federation of Gynecology and Obstetrics stage IB3-IIB who underwent NAT before radical surgery (NAT group = 94) or received surgical treatment alone (control arm = 32) was prospectively performed. All enrolled patients were clinically assessed with both a pelvic examination and MRI before surgical treatment. Data from the clinical examination were compared with the histopathological findings to assess the accuracy of MRI for staging purposes after NAT or before direct surgery. MRI showed an overall accuracy of 46.1%, proving it to be not superior to pelvic and physical examination. The overall MRI accuracy for the evaluation of parametrial, vaginal, and lymph node status was 65.8%, 79.4%, and 79.4%, respectively. In the NAT group, the accuracy for the detection of parametrial, lymph node, and vaginal involvement was lower than the control group; however, the difference was not significant (p ≥ 0.05). The overall accuracy of MRI for the preoperative staging of CC after NAT is shown to be not unsatisfactory. The limits of MRI staging are especially evident when dealing with pre-treated patients.

Lymph Node Metastases in Surgically Resected Solitary Ground-Glass Opacities: A Two-Center Retrospective Cohort Study and Pooled Literature Analysis.

An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter≤3cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR≤0.5 also had rare LN involvement (0.1%). From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤0.5. For the patients with GGO CTR >0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.

Abstract P4-02-06: Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization

Abstract Background: Over the last years, the management of patients with node positive early breast cancer has gone through important innovations. On the medical side, new targeted therapies such as olaparib and abemaciclib have been introduced, with promising results on the invasive disease-free survival. Moreover, sparing axillary lymph node dissection has proven to be noninferior in terms of overall survival. However, no tools are currently available to predict lymph node involvement before definitive surgical evaluation. The aim of the study was to analyze clinical and pathological characteristics of patients with node positive early breast cancer to explore potential risk profiles associated with a ≥3 nodal involvement. Methods: The study retrospectively analyzed 335 node-positive breast cancer patients treated at the Breast Unit of the CRO Aviano National Cancer Institute, between 2017 and 2021. Data regarding primary tumor biological features, lymph node involvement and surgical approach were collected. Associations between clinico-pathological characteristics and ≥3 lymph node involvement were tested through stepwise logistic regression and the gradient boosting machine learning algorithm (GBM). Results: Among the 335 analyzed patients, 87.0% had a primary tumor &amp;lt; 5 cm, with a single positive lymph node in 73.3% of cases. Hormone receptors were mainly positive (respectively 93.5% and 83.4% for estrogen and progesterone receptors). Tumor grade was most frequently well differentiated (Grade 1 in 60.7%), with a Ki67 &amp;lt; 20% (59.5%). After multivariable logistic regression, a tumor size ≥ 3 cm (OR 3.24, CI95% 1.47-7.17, p = 0.004), the presence of massive lymphovascular stromal invasion (OR 2.50, CI95% 1.02-6.14, p = 0.045) and 2 or more positive sentinel lymph nodes at surgical evaluation (OR 6.08, CI95% 3.34-11.05, p &amp;lt; 0.001) were associated with a higher risk of identifying ≥ 3 positive lymph nodes after subsequent axillary dissection. Similar results were observed in the luminal-like cohort. A GBM machine learning model was then developed with a 0.77 Area Under the Curve. Features with the highest relative importance (RI) were single sentinel node involvement (RI 16.1873), followed by tumor size ≥ 3 cm (RI 10.2024), ≥2 positive sentinel lymph nodes (RI 8.5050) and lymphovascular stromal invasion (4.0217). Consistently, number of positive sentinel lymph nodes and tumor size were the predominant features in all top 20 GBM models. Conclusions: The present study explored the definition of risk profiles linked to 3 or more positive lymph nodes based on clinical and pathological features. It, moreover, tested the feasibility of developing machine learning classifiers to support future clinical decision-making. Due to the growing complexity of the adjuvant setting, finding a balance between minimally invasive surgical and staging approaches and risk definition for treatment personalization will become increasingly critical. Citation Format: Tania Pivetta, Brenno Pastò, Martina Urbani, Elisabetta Benozzi, Nicola De Pascalis, Tiziana Perin, Mario Mileto, Bruno Pasquotti, Erica Piccoli, Lorenzo Vinante, Chiara Bampo, Silvia Bolzonello, Mattia Garutti, Milena Nicoloso, Serena Corsetti, Simona Scalone, Lucia da Ros, Paola di Nardo, Camilla Lisanti, Simon Spazzapan, Barbara Belletti, Michele Bartoletti, Lorenzo Gerratana, Samuele Massarut, Fabio Puglisi. Clinical and biological predictors of lymph node involvement in patients with early breast cancer for adjuvant treatment personalization [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-06.

Abstract P5-14-01: Transcriptomic insights into lobular breast cancer biology: a retrospective analysis of the MINDACT clinical trial

Abstract Background: Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer after invasive breast cancer of no special type (NST). In this retrospective analysis of the MINDACT trial, we aimed at identifying/refining the transcriptomic differences between: 1) estrogen receptor positive/HER2-negative (ER+/HER2-) ILC versus ER+/HER2- NST, 2) classic and non-classic ER+/HER2- ILC, and, 3) recurring and non-recurring ER+/HER2- ILC in the subgroup of patients with a low clinical and low genomic (cL/gL) risk (as defined by a modified version of Adjuvant Online! and the 70-gene signature). Patients and methods: Central pathology review was performed for histological subtype, grade and Ki67 (G.V.) for 5929/6693 (88.6%) of the patients included in the MINDACT trial (NCT00433589). Analysis of transcriptomic data adjusted for age and grade was performed using the R/Bioconductor package ‘limma’ to identify differentially expressed genes (DEGs). DEGs having absolute log-fold change (logFC)≥ 0.2 and FDR-adjusted p-value (q-value) &amp;lt; 0.05 were considered. Gene set enrichment analyses (GSEA) of MSigDB hallmark gene sets were performed. Adjusted Cox regression models were used to evaluate the association of these hallmarks with disease free survival (DFS) and distant recurrence free survival (DRFS). Results: After central pathological review, 464 patients with ER+/HER2- ILC and 3798 patients with ER+/HER2- NST were identified. Patients with ILC were significantly older at diagnosis, had larger tumors, less axillary nodal involvement, more grade 2 tumors than patients with NST. At the transcriptomic level, we observed a high number of DEGs between these 2 subgroups, confirming their distinct phenotype. CDH1, the gene coding for E-cadherin, was as expected the most highly overexpressed gene in NST versus ILC. We further observed an increased expression of leptin (LEP), leptin receptor (LEPR), lipoprotein lipase (LPL), and the fatty acid transporter CD36 in ILC. This could suggest that ILC relied on increased lipid uptake thanks to the increased contact of ILC tumor cells with the adipocytes. IGF1 was also overexpressed in ILC versus NST, as a potential consequence of high LEP and high LEPR expression. Differences were also evident with regard to the extracellular matrix (ECM), with many collagens, matrix metalloproteinases (MMPs) and other key enzymes (e.g. LOXL1) being differentially expressed. We confirmed a decreased ER-signaling and increased PI3K/Akt signaling in ILC versus NST. Out of the 464 ER+/HER2- ILC tumors, 253 (55%) were classic ILC and 211 (45%) non-classic ILC. There were more grade 3 tumors, more highly proliferative tumors and more nodal involvement in patients with non-classic versus classic ILC. At the transcriptomic level, differences were subtler than the differences seen above. Still, a significant enrichment of the hallmarks related to cell cycle in the non-classic ILC, and of the hallmarks related to epithelial-to-mesenchymal transition, hypoxia, adipogenesis and IL6/JAK/STAT3 signaling in classic ILC was observed. Finally, 216/464 patients with ER+/HER2- ILC (47%) were assigned to the cL/gL risk group and did not receive chemotherapy. 28/216 of these patients (13%) relapsed (DFS, median FU: 8.7 years). Enrichment of hallmarks related to apoptosis, inflammatory response, hypoxia and oncogenic signaling (PI3K/Akt, Ras, c-Myc) was associated with worse survival. Conclusion: This represents, to the best of our knowledge, the largest set of gene expression data for patients with ILC, issued from a clinical trial where histology was reviewed centrally. These results could be used to personalize treatment for patients with ILC. This project is funded by the Breast Cancer Research Foundation. Citation Format: Christine Desmedt, Ha-Linh Nguyen, François Richard, Sabine Linn, Otto Metzger, Coralie Poncet, Jelle Wesseling, Florentine Hilbers, Kim Aalders, Mauro Delorenzi, Suzette Delaloge, Jean-Yves Pierga, Etienne Brain, Suzan Vrijaldenhoven, Peter A Neijenhuis, Karen Van Baelen, Marion Maetens, Emiel Rutgers, Martine Piccart, Laura Van ’t Veer, Giuseppe Viale, Fatima Cardoso. Transcriptomic insights into lobular breast cancer biology: a retrospective analysis of the MINDACT clinical trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-01.

Lymphovascular invasion predicts lymph node involvement in patients with renal cell carcinoma

Lymphovascular invasion predicts lymph node involvement in patients with renal cell carcinoma

Neutrophil-to-lymphocyte ratio predicts nodal involvement in unfavourable, clinically nonmetastatic prostate cancer patients and overall survival in pN1 patients

The aim of our study was to determine the clinical utility of neutrophil-to-lymphocyte ratio (NLR) in predicting presence and prognosis of nodal involvement in patients treated with radical prostatectomy (RP) due to prostate cancer. This single-centre retrospective study included 205 patients treated with RP and lymphadenectomy between 2012 and 2018. Logistic regression and Kaplan–Meier analyses were performed to evaluate the prognostic value of preoperative NLR in terms of nodal spread and survival. Patients staged pN1 presented lower mean NLR (2.53 vs 3.86; p = 0.0025) compared to pN0 patients. On multivariable analysis of different haematological markers, only NLR exceeding the median (≥ 2.7) predicted pN1 (OR = 0.38; p = 0.0367) independently of biopsy grading and PSA. In internal validation (n = 31 pN1, n = 174 pN0) on the bootstrapped dataset using a spare cutoff of NLR ≥ 4.1 would allow sparing lymphadenectomy in 22.09% pN0 patients, missing 6.45% pN1 (NPV 92.66%; 95% CI 84.91–100%). Noticeably, in pN1 patients NLR ≥ 2.7 correlated with shorter overall survival (p = 0.0196), despite its association with reduced risk of pN1. High pre-prostatectomy NLR was negatively associated with pN1, yielding high NPV in internal validation. Simultaneously, high NLR in pN1 patients was associated with shorter survival.

Pathologic primary tumor factors associated with risk of pelvic and paraaortic lymph node involvement in patients with endometrial adenocarcinoma

The presence of lymph node (LN) positivity in endometrial adenocarcinoma (EAC) patients guides adjuvant treatment, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Primary pathologic tumor characteristics may predict risk of LN involvement in EAC patients with limited LN evaluation. Patients diagnosed between 2004–2016 with pathologic T1–T2 EAC in the National Cancer Database who had at least one lymph node sampled at the time of surgery were included. Pathologic primary tumor predictors of LN involvement were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN involvement, nomograms were generated. Among 57,810 EAC patients included, 4002 were node positive. On multivariable analysis, increasing pathologic tumor category (pT2 versus pT1a, odds ratio (OR) 5.43, 95% confidence interval (CI) 4.89–6.02, p &lt; 0.001), increasing pathologic tumor grade (grade 3 versus grade 1, OR 1.62, 95% CI 1.47–1.79, p &lt; 0.001), increase in tumor size per centimeter (OR 1.05, 95% CI 1.04–1.06, p &lt; 0.001), and presence of lymphovascular invasion (LVI) (OR 6.33, 95% CI 5.87–6.83, p &lt; 0.001) were predictive of overall LN positivity. The presence of LVI was a stronger predictor of paraaortic LN involvement (OR 6.43, 95% CI 5.55–7.47, p &lt; 0.001) than pelvic LN involvement (OR 5.42, 95% CI 4.98–5.90, p &lt; 0.001) in multivariable analysis. For patients with limited LN evaluation, pathologic tumor features can be used to estimate the risk of pelvic or paraaortic LN involvement. This information may inform adjuvant treatment decisions and guide future studies.