Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

The NILS study protocol - a retrospective validation study of a preoperative decision-making tool for non-invasive lymph node staging in women with primary breast cancer [ISRCTN14341750].

Background Routine preoperative axillary ultrasonography has proven insufficient for detecting low-burden nodal metastatic deposits. For the majority of newly diagnosed breast cancer patients presenting with clinical T1-T2 N0 disease, the standard axillary staging by sentinel lymph node biopsy is not therapeutic. The pilot non-invasive lymph node staging (NILS) artificial neural network (ANN) model to predict nodal status was published in 2019. The aim of the current study is to assess the performance measures of the model for the prediction of healthy lymph nodes in clinically N0 breast cancer patients at two breast cancer centers in Sweden. Methods This bicenter, observational, retrospective study has been designed to validate the NILS prediction model for nodal status using preoperatively collected clinicopathological and radiological data. A web-based implementation of the nodal status classifier has been developed and will be used in this study, resulting in an estimated probability of healthy lymph nodes for each study participant. Our primary endpoint is to report on the performance of the NILS prediction model to distinguish between healthy and metastatic lymph nodes (discrimination, N0 vs. N+) and compare the observed and predicted event rates of benign axillary nodal status (calibration). Discussion Internationally, there are numerous artificial intelligence projects involving non-invasive identification of N0 breast cancer. Here, we present a robust validation study based on external cohorts of our ANN model. Although validation is necessary to show generalizability, it is often overlooked. If the accuracy and discrimination reach a satisfactory level, our prediction tool can be implemented to assist medical professionals and breast cancer patients in shared decision-making on omitting sentinel node biopsy in patients predicted to be node-negative. In future, this may potentially save healthcare resources and reduce costs and adverse side effects. In addition, our study might prompt future studies of nodal metastases of malignancies in other organs, and thus might have implications beyond breast cancer. Trial registration This study has been prospectively registered in the ISRCTN registry, identification number: 14341750

STUDY OF CORRELATION OF INFLAMMATORY CELL INFILTERATION SCORE WITH TUMOR GRADE, NODAL STATUS, ER, PR, HER-2 NEU STATUS IN PATIENTS OF STAGE 2 AND 3 BREAST CANCER IN A TERTIARY CENTER, KOLKATA

Breast Cancer is the most common cancer in women in India and constitute one–third of women’s cancers and is second reason of mortality after lung carcinoma.[1] It is the most commonly diagnosed malignancy in most cities in India, and 2nd most common cancer in females in the rural areas. As the disease burden and mortality rate is very high, evaluation of several parameters that influence survival rates among women with breast cancer may help design early detection, predict the prognosis and frame a suitable line of treatment.[2] The link between inflammation and cancer was first suggested in 1863.[3] Chronic inflammation is known to increase the risk of cancer development, such as colon cancer in inflammatory bowel diseases.[4] There is good evidence that the development of cancer and its progression are dependent on a complex interaction of the tumour and the host inflammatory response.[5] Aim: This study aims to correlate the relation of inflammatory cell infilteration with tumour staging, nodal status, ER, PR, HER-2 NEU status of breast cancer. Material and Method: The proposed study was a cross sectional study with mostly prospective observation and with some retrospective observation, included 74 patients of stage II and stage III breast carcinoma who underwent MRM in Cancer Institute from 2017-2018. The various clinical and histopathological prognostic parameters along with inflammatory cell infilterate score in invasive breast carcinoma patients were studied and correlated. The inflammatory cell infilterates was assessed according to Klintrup-Makinen (K-M) criteria. It is scored on 4 point scale where score 0 defined no increase in inflammatory cell infilterate, score 1 defined as mild or patchy increase ,score 2 denoted as prominent inflammatory response with some cancer cell destruction and score 3 as florid cup like response. Further it is classified as low group score (score 0-1)and high group score (score 2-3) .[6] Result: There was significant association between inflammatory cell infiltrate score and grade of tumor (p=0.0005) (TABLE 1) .58.1% ,54.1% and 37.8% of the cases were ER, PR and Her-2/neu positive respectively. ER negative tumors (74.19%) were showing statistically significant (p= 0.01) association with high inflammatory cell infilterate score (ie. Score 2 and 3). Similarly PR negative tumors (64.7%) were showing statistically significant association (p= 0.04) with high inflammatory cell infilterate score. No such correlation was found between between HER-2 /NEU status and nodal involvement with inflammatory cell infilterate score (TABLE 3). Keywords: Breast cancer, Invasive ductal carcinoma, ER , PR , HER-2/Neu ,grade of tumor, Nodal status, inflammatory cell infilterate score.

Toward an Optimized Staging System for Pancreatic Ductal Adenocarcinoma: A Clinically Interpretable, Artificial Intelligence–Based Model

PURPOSE The American Joint Committee on Cancer (AJCC) eighth edition schema for pancreatic ductal adenocarcinoma treats T and N stage as independent factors and uses positive lymph nodes (PLNs) to define N stage, despite data favoring lymph node ratio (LNR). We used artificial intelligence–based techniques to compare PLN with LNR and investigate interactions between tumor size and nodal status. METHODS Patients who underwent pancreatic ductal adenocarcinoma resection between 2000 and 2017 at six institutions were identified. LNR and PLN were compared through shapley additive explanations (SHAP) analysis, with the best predictor used to define nodal status. We trained optimal classification trees (OCTs) to predict 1-year and 3-year risk of death, incorporating only tumor size and nodal status as variables. The OCTs were compared with the AJCC schema and similarly trained XGBoost models. Variable interactions were explored via SHAP. RESULTS Two thousand eight hundred seventy-four patients comprised the derivation and 1,231 the validation cohort. SHAP identified LNR as a superior predictor. The OCTs outperformed the AJCC schema in the derivation and validation cohorts (1-year area under the curve: 0.681 v 0.603; 0.638 v 0.586, 3-year area under the curve: 0.682 v 0.639; 0.675 v 0.647, respectively) and performed comparably with the XGBoost models. We identified interactions between LNR and tumor size, suggesting that a negative prognostic factor partially overrides the effect of a concurrent favorable factor. CONCLUSION Our findings highlight the superiority of LNR and the importance of interactions between tumor size and nodal status. These results and the potential of the OCT methodology to combine them into a powerful, visually interpretable model can help inform future staging systems.

Elucidating the clinical-pathological factors and prognosis in breast cancer young surviving women who had a subsequent pregnant

Objective. To elucidate the impact of clinical-pathological factors on overall survival (OS) in patients who got pregnant after breast cancer treatment. Methods. Retrospective cohort of women age younger than 40 years with breast cancer history without active disease at diagnosis of postcancer pregnancy. Clinical-pathological factors were analized by age group and recent birth. Overall survival (OS) was evaluated from Kaplan-Meier method. The association between clinical-pathological factors and OS was examined using Cox proportional hazards method to estimate hazard ratio (HR) with 95% confidence intervals (CI). Results: A total of 14 patients were selected. Median age was 28.5 years (interquartile range, 26-35). Locally advanced stage (IIB-IIIB) was diagnosed in 64.3%. Patients lower than 35 years experienced more positive clinical lymph nodes (72.7%), grade 2 (63.6%) and ER/PgR-negative tumors (54.5% and 72.7%, respectively). The patients with ER-positive tumors showed an improvement non-significant at 5-year OS (87%; p = 0.097). In the bivariate analysis, patients with a higher number of pathological lymph nodes (pNs) had a 12% increase in the risk of death than those with lower number (HR = 1.12; 95% CI: 1.02 to 1.2). The multivariate model (after adjustment for number of pNs, age and tumor size) ascertained that the nodal status was the only independent predictor associated to a worse OS (HR = 1.15; 95% CI: 1.01 to 1.3). Conclusion. Pregnancy after cancer did not have a detrimental effect on survival. The patients < 35 years old group showed more unfavorable tumor features at diagnosis, which can largely explain a poorer prognosis. Nodal status was the most important prognostic factor that predicted the poor prognosis.

Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes – Risk Pattern and Outcomes on a Community Level

Introduction The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX) in patients with 0-3 lymph nodes in a high volume community hospital. Methods Patients with non-metastatic HR+/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX testing were included in this retrospective study. The distribution of clinico-pathologic characteristics, recurrence score (RS) risk and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease free survival (DFS) and overall survival (OS) were estimated. Results From 2012 to2017 ODX was consecutively performed in 575 (16.4%) of 3492 women with HR+/ HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had a RS of 0 to 25 and 112 (20.3%) had a RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5y-DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p= 0.101) or OS (97.2% vs. 96.0%; p= 0.737) for patients with a RS 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions The results of the study confirm the observations from randomized studies on the use of the ODX in a real world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR+/HER2- breast cancer with 0-3 positive lymph nodes and RS<25.

To Look or Not to Look? Yes to Nodal US!

Knowledge of axillary nodal status is highly important for correct staging and treatment planning in patients with breast cancer. Axillary US is a recognized highly specific and cost-effective tool for assessing nodal status and guiding appropriate treatment. Axillary US imaging with US-guided biopsy is routinely performed throughout the world. However, because of recent developments in the surgical management of the axilla in patients with newly diagnosed breast cancer (American College of Surgeons Oncology Group [ACOSOG] Z0011 trial) and in patients with breast cancer receiving neoadjuvant systemic therapy (ACOSOG Z1071, SENTinel NeoAdjuvant [SENTINA] and Sentinel Node biopsy aFter NeoAdjuvant Chemotherapy [SN FNAC] trials), some have questioned the utility of axillary US for nodal staging. Here, we review the evidence to date supporting the additional value of axillary US for patients with breast cancer. Nodal US in patients with newly diagnosed breast cancer is useful for staging; in a significant proportion of patients, nodal US identifies additional axillary level II or level III nodal disease, which allows for appropriate treatment of disease. Furthermore, ongoing clinical trials may show that axillary surgery can be omitted in patients with negative findings on axillary US. In patients with lymph node–positive disease undergoing neoadjuvant systemic therapy, nodal US can guide the approach to axillary surgery. A more personalized patient approach, taking into the account tumor biology, among other factors, may help to mitigate the controversy surrounding the role of axillary US in breast cancer patients.