Sentinel Lymph Node Involvement Research Articles

Abstract PO3-23-07: Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients

Abstract Background: Axillary surgery is now routinely de-escalated in clinically node negative breast cancer patients with limited axillary nodal burden (up to 2 involved sentinel nodes) based on the results of ACOSOG-Z0011 and AMAROS trials. However, patients with proven axillary metastasis following on ultrasound (AUS) guided core needle biopsy (CNB), undergoing primary surgery are still subjected to an axillary lymph node dissection (ALND) irrespective of the magnitude of the axillary nodal burden. If we could predict axillary nodal burden with a low false negative rate (FNR) for the presence of extensive axillary nodal involvement, we can then hypothesize that axillary surgery could be safely de-escalated in this cohort of patients. We investigated whether pre-operative AUS suggesting limited axillary burden is sensitive enough to rule out gross axillary disease burden. Methods: A single institution retrospective study. We undertook an electronic chart review of all T1 to T3 patients undergoing upfront ALND with either mastectomy or breast conserving surgery between January 2019 and June 2023. Patients with palpable axillary nodes, locally advanced breast cancer or a completion ALND after positive sentinel lymph node biopsy (SLNB) were excluded from the study. Clinical and pathological characteristics associated with nodal burden of disease were evaluated. Limited axillary burden was defined as < 2 involved nodes with ≥3 taken as gross nodal burden for primary analyses. Sensitivity analyses were carried out with limited axillary burden defined as < 3 involved nodes (N1) and ≥4 (N2) taken as gross nodal burden. Subgroup analyses in T1 or T2 tumors were carried out as well. The probabilities of discordant events, defined as limited burden on AUS-CNB but gross burden on final histopathology evaluation (HPE), assuming 10% FNR, were estimated using inverse cumulative binomial distribution function. Results: Data on the exact number of suspicious nodes on AUS were missing for 2 patients, therefore, the final study cohort included 39 patients. The correlation between AUS nodal burden and that on HPE was moderate (Spearman’s rho = 0.48; p = 0.0018). The sensitivity and specificity of AUS in identifying gross nodal burden were 61% and 81% respectively. Observation of 9 discordant events in 22 patients with low burden on AUS ruled out an FNR of < 10% with 99.99% certainty. The sensitivity and specificity in T1/T2 subgroup were 60% and 75% respectively. The sensitivity analyses classifying N1 as limited and N2 as gross axillary burden showed the sensitivity and specificity of 35% and 82% respectively and an FNR of < 10% was ruled out with 99.996% certainty. Conclusion: Pre-operative AUS alone lacks the sensitivity and specificity to accurately predict the true axillary nodal burden to safely guide de-escalation of axillary surgery. AUS followed by targeted axillary dissection (TAD) in conjunction with a dual technique SLNB may provide the desired sensitivity and specificity to guide de-escalation of axillary surgery. A prospective evaluation of this approach is merited. Given the limited number of patients that could be enrolled in such prospective study from individual institutions, an international collaborative effort is needed to address this important research question. Citation Format: Nidhi Garg, Mangesh Thorat, Hisham Hamed, Ashutosh Kothari. Evaluation of the role of axillary ultrasound to estimate axillary nodal burden to guide de-escalation of upfront axillary surgery in node positive early breast cancer patients [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 PO3-23-07.

Prognostic significance of sentinel lymph node biopsy in elderly with cutaneous melanoma: systematic review and meta-analysis.

Sentinel lymph node biopsy is the most powerful prognostic indicator to date for cutaneous melanoma. Even though elderly patients have a lower incidence of sentinel node involvement, its results are still necessary for access to adjuvant therapies. This is highly relevant considering that the Western population shows an aging trend, and the incidence of melanoma has grown exponentially over the years, making elderly patients more likely to die from melanoma than younger ones. We performed a systematic review to investigate the prognostic significance of sentinel lymph node biopsy in elderly patients with melanoma. The systematic review was conducted following the PRISMA guidelines and registered in PROSPERO. The authors searched the Cochrane Database, EMBASE, PubMed, and WOS. Eligible studies for the systematic review were clinical trials, observational population studies, clinical or hospital-based cohort studies, and case-control studies. The meta-analysis was conducted using the R software program applying the meta package. Six reports were identified to meet the inclusion criteria. All studies were retrospective, non-randomized cohorts. The results obtained in this systematic review show a statistically significant influence of sentinel lymph node biopsy on disease-specific survival (HR = 2.87; 95% CI: 1.73-4.74) but also suggest that a positive result negatively impacts disease-free survival (HR = 3.41; 95% CI: 0.96-12.11). This meta-analysis shows that a positive sentinel lymph node biopsy does not imply differences in overall survival but significantly influences disease-specific survival and suggests an unfavorable impact on disease-free survival.

Accuracy of sentinel node mapping in Marjolin ulcer: Comparison of three different injection techniques

BackgroundMarjolin ulcer is a specific type of squamous cell cancer that can benefit from the use of lymphoscintigraphy.The purpose of this study was to evaluate 3 different injection techniques for sentinel node biopsy in patients with Marjolin ulcer. MethodsForty-eight patients with Marjolin ulcer (27 male and 21 female) ranging in age from 24 to 85 years were included in our study. Intratumoral (IT), peritumoral (PT) and periscar (PS) tissue injections of radiotracer were done in 9, 10, and 29 patients respectively. Injections were done 2–4 h before surgery. Lymphoscintigraphy was done for mapping the lymphatic drainage. During surgery, lymphatic mapping and sentinel node biopsy was performed using a handheld gamma probe. After harvesting sentinel nodes, regional lymph node dissection was done. ResultSentinel node detection rate was higher in the PS group as compared to the IT and PT groups (89.6% vs. 50% and 22.2%) respectively. False negative rate was 0%. Pathologically involved sentinel nodes were detected in 16% of the included patients of our study which led to management change. None of the patients with pathologically non-involved sentinel nodes developed regional lymph node recurrence. ConclusionLymphatic mapping and sentinel node biopsy is feasible in Marjolin ulcer with high detection rate and low false negative cases which by detection of regional lymph node involvement can potentially change the management of patients. Injection site may be an important factor influencing the success of the procedure and injection of the mapping material in the peri-scar normal skin proximal to the lesion is the best technique.

The Sentinel Node and Occult Lesion Localization (SNOLL) Technique Using a Single Radiopharmaceutical in Non-palpable Breast Lesions.

In order to perform a full surgical resection on non-palpable breast lesions, a current method necessitates correct intraoperative localization. Additionally, because it is an important prognostic factor for these patients, the examination of the lymph node status is crucial. The aim of this study was to evaluate the efficiency of the sentinel node and occult lesion localization (SNOLL) technique in localizing nonpalpable breast lesions together with sentinel lymph node (SLN) using a single radiotracer, that is, nanocolloid particles of human serum albumin (NC) labeled with technetium-99m (99mTc). 39 patients were included, each having a single non-palpable breast lesion and clinically no evidence of axillary disease. Patients received 99mTc- NC intratumorally on the same day as surgery under the guidance of ultrasound. Planar and single-photon emission computed tomography/computed tomography lymphoscintigraphy were performed to localize the breast lesion and the SLN. The occult breast lesion and SLN were both localized using a hand-held gamma-probe, which was also utilized to determine the optimal access pathway for surgery. In order to ensure a radical treatment in a single surgical session and reduce the amount of normal tissue that would need to be removed, the surgical field was checked with the gamma probe after the specimen was removed to confirm the lack of residual sources of considerable radioactivity. Breast lesions were successfully localized and removed in all patients. Pathological findings revealed breast carcinoma in 11/39 patients (28%) and benign lesions in 28 (72%). Axillary SLNs were detected in 31/39 (79.5%) patients. The metastatic involvement of SLN was only seen in two cases. While the identification rate of the SNOLL technique performed with an intratumoral injection of 99mTc-NC as the sole radiotracer in non-palpable breast lesions was great, it was not fully satisfactory in SLNs.

Prediction of sentinel lymph node metastasis in breast cancer patients based on preoperative features: a deep machine learning approach

Sentinel lymph node (SLN) biopsy is the standard surgical approach to detect lymph node metastasis in breast cancer. Machine learning is a novel tool that provides better accuracy for predicting positive SLN involvement in breast cancer patients. This study obtained data from 2890 surgical cases of breast cancer patients from two referral hospitals in Iran from 2000 to 2021. Patients whose SLN involvement status was identified were included in our study. The dataset consisted of preoperative features, including patient features, gestational factors, laboratory data, and tumoral features. In this study, TabNet, an end-to-end deep learning model, was proposed to predict SLN involvement in breast cancer patients. We compared the accuracy of our model with results from logistic regression analysis. A total of 1832 patients with an average age of 51 ± 12 years were included in our study, of which 697 (25.5%) had SLN involvement. On average, the TabNet model achieved an accuracy of 75%, precision of 81%, specificity of 70%, sensitivity of 87%, and AUC of 0.74, while the logistic model demonstrated an accuracy of 70%, precision of 73%, specificity of 65%, sensitivity of 79%, F1 score of 73%, and AUC of 0.70 in predicting the SLN involvement in patients. Vascular invasion, tumor size, core needle biopsy pathology, age, and FH had the most contributions to the TabNet model. The TabNet model outperformed the logistic regression model in all metrics, indicating that it is more effective in predicting SLN involvement in breast cancer patients based on preoperative data.

A convolution neural network for rapid and accurate staging of breast cancer based on mammography

IntroductionBreast cancer (BC) has been one of the main reasons for women's deaths in the recent decade. This study hypothesizes that the deep features resulting from mammography staging can be used to determine tumor staging and lymph nodes of the sentinel lymph node (SLN) before surgery in BC patients. MethodsA retrospective study of female BC patients being treated. Pathological variables were collected from medical records, including age, tumor location, staging based on the American Joint Committee on Cancer (AJCC), pathological type, human epidermal growth factor receptor 2 (HER2) status, Progesterone Receptor (PR) status, and Estrogen Receptor (ER) status. The contrast enhancement technique with Contrast-Limited Adaptive Histogram Equalization (CLAHE) was applied to the studied data using MATLAB software. The images were first changed from color to gray in the preprocessing process, and then the images were changed from gray to color again. The regions of interest (ROI) of the primary tumor were isolated from other areas of breast tissue by two expert radiologists. Therefore, a proposed convolution neural network (CNN) model was applied. ResultsIn this study, 390 patients' information was used to analyze the data. In total, out of 390 patients, 300 had metastatic SLN involvement, and 390 had a tumor size greater than 1 mm. Performance evaluation of the proposed CNN staging was AUC 0.919 (95 % CI: 0.852,0.971) for the training group and AUC 0.877 (95 % CI: 0.805,0.949) for the validation group. ConclusionsThis study proposes a deep learning model based on CNN based on mammographic images, which has a suitable function for determining tumor staging and SLN metastasis.

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial).

Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results. ClinicalTrials.gov, identifier number NCT04889924.

Influence of follow-up time on outcome of children and adolescents with atypical Spitz tumor/Spitz melanoma (AST/SM): Results from the MACMEL registry.

e21558 Background: Pediatric melanoma is a rare and challenging diagnosis, requiring an integrated clinicopathologic and genomic approach to optimize diagnosis and clinical care. The Molecular Analysis of Childhood Melanocytic Tumors (MACMEL) registry (Pappo A Cancer. 2021 Oct 15;127(20):3825-3831) was developed to better characterize pediatric melanocytic lesions by including clinical information, central pathology review, and genomic analysis. The AST/SM subtype of melanocytic lesions often affects younger patients, have a high incidence of nodal involvement, and are genomically characterized by copy number aberrations and kinase fusions. Methods: A review of the MACMEL registry data for patients with AST/SM enrolled from May 2016 to December 2022. Patient data included demographics (age, sex, ethnicity), anatomic location of lesion, sentinel node involvement, AJCC staging, genomic and germline findings, therapy, and disease outcomes. Results: We identified 60 patients with AST (n=17) and SM (n=43). 28 patients had stage III disease and 16 had stage IIIC disease. There were 38 females, and 22 males. The most common primary sites were the extremities and the most common gene rearrangements included MAP3K8 (n= 10) and ALK (n= 12). Other genomic alterations identified included kinase fusions NTRK, ROS1, BRAF, FLOT2-ARAF, RAC1, BRIP1, SDHAF2, ATM, GPNMB-ERBB2, and CDKN2B. None of the 55 patients that underwent TERT promoter analysis had a mutation. Adjuvant treatment was given to 8 patients (interferon 3, pembrolizumab 4, larotrectinib 1). The median follow-up time for the cohort is 3.1 years, with 57 patients alive with no evidence of disease. 1 patient had a local relapse treated with wide local excision and is currently alive with no evidence of disease. 3 patients were lost to follow up. Event free survival (EFS) for the cohort is 98% and overall survival (OS) is 100%. Conclusions: Patients with AST/SM comprise the largest subtype of melanocytic lesions enrolled on the MACMEL registry and have an excellent clinical outcome. This supports our previous observations that patients with AST/SM who lack TERT promoter mutations may be able to be managed conservatively and that an integrated diagnostic approach incorporating genomic information is vital for optimal diagnosis and clinical management. [Table: see text]

Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator

To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n=131); luminal B, 19.1% (n=40); HER2 enriched 13.4% (n=28); and triple negative, 4.8% (n=10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Abstract P4-03-44: A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center

Abstract Male breast cancer is a rare disease accounting for less than 1% of all breast cancer diagnosis. Male breast cancers occur later in life and are more estrogen receptor-positive compared to female breast cancers. Breast cancer in men is often diagnosed later and survival rates are lower than in female cases. The aim of this retrospective study is to analyze the epidemiological, clinical and therapeutic data of all male breast cancer cases over the span of 11 years to at Methodist Dallas Medical Center between 2010 – 2021. During this time period, there was a total of 1,784 cases of breast cancer diagnosed. There were 8 cases male breast cancers, accounting for 0.45% of all breast cancer cases. The average age of diagnosis was 69.5 years old. The most common type of male breast cancer was invasive ductal carcinoma with 7 cases (87.7%). The remaining 1 case (12.5%) were ductal carcinoma in situ (DCIS). 100% of our male breast cancer cases were estrogen receptor and progesterone receptor positive. No male breast cancer case had Her2/Neu receptor over-expression. Of all male breast cancer cases, 75% had a family history of cancer suggesting that genetic factors play a significant role in the development of breast cancer in men. At time of diagnosis, 4 cases (50 %) were staged at cT4 and the remainder of cases were between cT0 - cT2. 37.5% of all cases had sentinel lymph node involvement at time of diagnosis. From the time period of 2010 – 2014 there were no incidences of male breast cancer; however, from 2015 – 2021 there were 8 total cases. There were 2 cases (25%) of death. Number of Male Breast Cancer Cases by Year Number of Male Breast Cancer Cases by Year Number of male breast cancer cases diagnosed by year at Methodist Dallas Medical Center Epidemiological and Clinical Data of Male Breast Cancer Cases Citation Format: Huy Nong, Vasu Moparty, Atisha Manhas. A Case Series of Male Breast Cancer Patients at Methodist Dallas Medical Center [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 P4-03-44.

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 < 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 < 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 < 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.

Incidence of endometrial carcinoma in patients with endometrial intraepithelial neoplasia versus atypical endometrial polyp

ObjectiveOur study’s primary aim was to compare the incidence of endometrial carcinoma in patients with a presurgical diagnosis of endometrial intraepithelial neoplasia confined to the endometrium (EIN-E) versus endometrial intraepithelial...

Preoperative predictive factors affecting sentinel lymph node positivity in breast cancer and comparison of their effectiveness with existing nomograms.

This study aimed to establish a strong regression model by revealing the preoperative predictive factors for sentinel lymph node (SLN) positivity in patients with early stage breast cancer (ESBC). In total, 445 patients who underwent SLN dissection for ESBC were included. All data that may be potential predictors of SLN positivity were retrospectively analyzed. Tumor size >2 cm, human epidermal growth factor receptor 2 (HER2) + status, lymphovascular invasion (LVI), palpable tumor, microcalcifications, multifocality or multicentricity, and axillary ultrasonographic findings were defined as independent predictors of SLN involvement. The area under the receiver operating characteristic (ROC) curve (AUC) values were 0.797, 0.808, and 0.870 for the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram, MD Anderson Cancer Center (MDACC) nomogram, and our regression model, respectively (P < .001). The recent model for predicting SLN status in ESBC was found to be stronger than existing nomograms. Parameters not included in current nomograms, such as palpable tumors, microcalcifications, and axillary ultrasonographic findings, are likely to make this model more meaningful.

The need to tailor the omission of axillary lymph node dissection to patients with good prognosis and sentinel node micro-metastases.

Results of IBCSG-23-01-trial which included breast cancer patients with involved sentinel nodes (SN) by isolated-tumor-cells or micro-metastases supported the non-inferiority of completion axillary-lymph-node-dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN-micro-metastases. To investigate the impact of cALND omission on disease-free-survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission. Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value=0.002) and borderline significant differences in DFS (p-value=0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR=2.77, CI95%=1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND. Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time.

Primary diffuse large B-cell lymphoma of the uterus – A case report

Extranodal non-Hodgkin’s lymphoma (NHL) constitutes one fifth to one third of all cases of NHL. Secondary lymphomatous involvement of the female genital tract (FGT) is not rare and is often seen in disseminated disease; however, primary NHL of the FGT is extremely rare. The uterine corpus is only third to the ovaries and uterine cervix as a site for primary NHL of the FGT. Differentiation between primary and secondary involvement of FGT organ by a haematolymphoid neoplasm relies upon the localisation versus dissemination of the disease at time of diagnosis. We report a case of a 71-years-old lady with primary diffuse large B-cell lymphoma (DLBCL) of the uterine corpus. The histology showed a diffuse infiltrate of large atypical discohesive cells associated with multinucleated tumour cells and brisk mitosis. A panel of immunohistochemical stains showed results consistent with the diagnosis of DLBCL made on routine stains. There was only one involved sentinel node, and radiologically there was no evidence of other involved sites by lymphoma. Designation of the lymphoma as primary to the FGT is clinical and having appropriate imaging studies of the patient is vital for this purpose.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

PurposeAs clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. MethodsSLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). ResultsThe median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. ConclusionCentral review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Histopathological growth distribution of ductal carcinoma in situ: tumor size is not "one size fits all".

Ductal carcinoma in situ (DCIS) is a group of preinvasive breast neoplasms. Studies have shown excellent survival among patients with lumpectomy-amenable disease. Patients requiring mastectomy have been less well characterized. We aim to characterize this cohort and identify whether growth distribution pattern is associated with sentinel lymph node involvement at time of surgery or subsequent development of metastatic disease. Patients were identified using local cancer registry data and were chart reviewed using electronic medical records. Growth pattern was classified as unifocal, multifocal, or diffuse. Chi-squared, Analysis of Variance (ANOVA), and Kaplan-Meier analyses were performed. Two hundred and twenty-six patients were identified with median age at diagnosis 49 and follow up 7.1 years. 42 had unifocal, 51 had multifocal and 20 had diffuse lesions. 3/20 patients with diffuse type lesions developed subsequent distant metastatic disease, while none of the patients with unifocal or multifocal lesions did. 1/20 patients with diffuse and 2/51 with multifocal disease had sentinel lymph node involvement (SLNI) at surgery. Tumor extent was not associated with sentinel lymph node involvement or distant metastatic disease (P=0.2, Kaplan-Meier analysis) but growth pattern was (P=0.01). It was also associated on Kaplan-Meier with development of distant metastatic disease alone (P=0.01). Patients with diffuse growth pattern DCIS were more likely to have SLNI or development of distant metastatic disease. Our findings suggest that patients with diffuse type lesions are at greater risk of metastatic disease and therefore breast cancer death from DCIS. Optimal therapy for these patients will need further elucidation.

Melanoma trials that defined surgical management.

Treatment of regional lymph nodes in melanoma has been controversial for more than a century. A series of clinical trials evaluating elective lymph node dissection and then sentinel lymph node biopsy have helped define the current standard of care. These trials resulted in increasingly selective application of surgical intervention for regional lymph nodes in melanoma. First by focusing on optimal candidates for elective lymph node dissection and then by identifying patients through sentinel lymph node biopsy. The current standard of sentinel lymph node biopsy for appropriately selected patients and nodal observation for many patients, even with involved sentinel nodes is both more accurate in staging and much less morbid than what came before.

Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient’s and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient’s eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient’s and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.

Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).

BackgroundInformation regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1–2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC.MethodsWe retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC.ResultsA total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1–2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1–2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant.ConclusionsPatients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1–2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1–2 positive SLNs.