Node Tumor Burden Research Articles

Abstract PO5-17-09: Event-free survival in HER2-low vs HER2-zero breast cancer patients submitted to neoadjuvant chemotherapy

Abstract Background: Breast cancer (BC) with low expression of HER2 (HER2-low) might constitute a group of tumors with unique clinical and biological characteristics. However, the prognostic impact of HER2-low status vs HER2-zero in terms of pathological complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy (NACT) remains controversial. The aim of this study was to evaluate pCR and EFS rates in HER2-low vs HER2-zero early BC patients treated with NACT. Methods: In this cross-sectional study, we analyzed 565 consecutive patients with HER2-low and HER2-zero early BC submitted to neoadjuvant therapy from 2017 to 2021 in a single academic center. Patients with biopsy-confirmed stage I-III BC, with HER2-low or HER2-zero status, submitted to locoregional therapy after NACT were included. Clinical and pathological characteristics, pathological response, treatment protocol and RFS were analyzed and considered for statistical analysis. HER2-low was defined by IHC 1+, or 2+ ISH non-amplified; HER2-zero was defined by IHC 0. Pathological response was determined locally, and pCR defined as the absence of residual invasive disease with or without ductal carcinoma in situ in the breast and axilla. EFS was defined as the time from diagnosis to distant recurrence, a second primary, or death from any cause, whichever occurred first. Results: 441 patients were included in the analysis, 236 (53.5%) patients with HER2-low tumors, and 205 (46.5%) with HER2-zero tumors. Overall, 279 (63.3%) were estrogen receptor (ER)-positive tumors, and 162 (36.5%) were ER-negative tumors. Among ER-positive tumors, 166 (59.5%) had HER2-low status, and 113 (40.5%) were HER2-zero. For the ER-negative subgroup, the corresponding rates were 70 (43.2%) and 92 (56.8%), respectively. Most patients had stage II-III BC (423/441; 96%), and 20.2% (89/441) had high nodal tumor burden. Many patients received anthracycline- and taxane-based NACT (425/441; 96.4%), and over 90% (148/162; 91.3%) of ER-negative patients received a platinum agent. The overall pCR rate were 18.1%. Among ER+ tumors, pCR rates were 6.4%, 6.0%, and 7.0% in the overall, HER2-low and HER2-zero tumors, respectively. In ER- tumors, the corresponding pCR rates were 38.3%, 35.7, and 40.2%, respectively. The differences in pCR rates between HER2-low and HER2-zero tumors were not statistically significant (ER-positive, p=0.724; ER-negative, p=0.559). After a median follow-up of 42 months, 90 EFS events occurred. In the HER2-low group there were 56 (23.7%) EFS events, and 34 (16.6%) EFS events in the HER2-zero (HR 1.19; 95% CI 0.77-1.82; p=0.427). Among 279 patients in the ER-positive group there were 48 events, 32 in the HER2-low subgroup and 16 in the HER2-zero group (HR 1.16; 95% CI 0.64-2.13; p=0.622). Among 162 ER-negative tumors there were 42 events, 24 in the HER2-low subgroup, and 24 in the HER2-zero subgroup (HR 1.56; 95% CI 0.84-2.88; p=0.158). NACT discontinuation occurred in 86 patients (ER-positive: 45, 16.1%; ER-negative: 41, 25.3%), mainly due to toxicity (anthracycline-taxane: 10.0%; platinum: 11.7%). Disease progression during NACT were reported in 6.8% (30/441) of patients. Conclusions: Our results show similar pCR rates and RFS among HER2-low and HER2-zero early BC patients after standard NACT, which are consistent with the current literature. Despite the predictive role of low HER2 expression in selecting patients for novel antibody-drug conjugates (ADCs) therapy, its prognostic value could not be confirmed. Citation Format: Guilherme Sartori, Susana Ramalho, Leonardo Roberto da Silva, Tomás Reinert, Mahira Lopes Da Rosa, Grazielle Morais Tavares, Vivian Vasconcelos, Higor Mantovani, Ana Elisa Ribeiro Da Silva Cabello, Guilherme Coelho, Jovana Mandelli, Facundo Zaffaroni, César Cabello, Carlos Barrios, Marcia Silveira Graudenz. Event-free survival in HER2-low vs HER2-zero breast cancer patients submitted to neoadjuvant chemotherapy [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 PO5-17-09.

Abstract SY12-01: Targeting validated but un-drugged oncogenes with small molecule protein degraders

Abstract SY12-01: Targeting validated but un-drugged oncogenes with small molecule protein degraders

Sentinel lymph node assessment in melanoma: current state and future directions.

Assessment of sentinel lymph node status is an important step in the evaluation of patients with melanoma for both prognosis and therapeutic management. Pathologists have an important role in this evaluation. The methodologies have varied over time, from the evaluation of dimensions of metastatic burden to determination of the location of the tumour deposits within the lymph node to precise cell counting. However, no single method of sentinel lymph node tumour burden measurement can currently be used as a sole independent predictor of prognosis. The management approach to sentinel lymph node-positive patients has also evolved over time, with a more conservative approach recently recognised for selected cases. This review gives an overview of past and current status in the field with a glimpse into future directions based on prior experiences and clinical trials.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6weeks, 6-12weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection.

Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS). Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed. We recorded metrics to quantify LN tumor burden. We also characterized the LN anatomical compartments involved and quantified the extent of ENE. The median follow-up time was 38 months. The median number of total LNs obtained per patient was 30 (IQR 23-37). In the risk-adjusted cox regression model, the following variables were associated with BRFS: mean size of the largest LN deposit per patient (log2: adjusted hazard ratio (aHR) = 1.91, p < 0.001), the mean total span of all LN deposits per patient (2.07, p < 0.001), and the mean percent surface area of the LN involved with the tumor (1.58, p < 0.001). There was no significant BRFS association for the LN anatomical compartment or the quantified extent of ENE. LN tumor burden is associated with BRFS. The LN anatomical compartments and the quantified extent of ENE did not show significant association with BRFS.

Detection of ctDNA in patients with stage III cutaneous melanoma with satellite/in-transit or nodal metastases.

e21559 Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker to monitor disease status in cancer patients. Limited data exists on the sensitivity of ctDNA for detection of satellite/in-transit or nodal metastases in melanoma. Methods: We conducted a retrospective study of stage III cutaneous melanomas with clinically detected satellite/in-transit and/or lymph node metastases who underwent ctDNA analysis using an mPCR-NGS-based ctDNA assay ("Signatera") prior to surgery or systemic therapy at Inova Schar Cancer Institute. Results: ctDNA was detected in 4 of 14 patients including 1 of 3 patients with both satellite/in-transit metastases and nodal metastases; 3 of 6 patients with nodal metastases only; none of 5 patients with satellite/in-transit metastases only. Nodal tumor burden (sum of short axis of involved lymph nodes) for ctDNA detected patients was greater than 1.5cm (5.0cm, 3.0cm, 3.0cm, and 1.6cm, respectively), and 1.5cm or less in patients whose ctDNA were not detected. Conclusions: ctDNA may not detect satellite/in-transit metastases or small nodal metastases in melanoma. A larger study is needed to validate this finding. [Table: see text]

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

Automated Breast Ultrasound (ABUS)-based radiomics nomogram: an individualized tool for predicting axillary lymph node tumor burden in patients with early breast cancer

ObjectivesPreoperative evaluation of axillary lymph node (ALN) status is an essential part of deciding the appropriate treatment. According to ACOSOG Z0011 trials, the new goal of the ALN status evaluation is tumor burden (low burden, < 3 positive ALNs; high burden, ≥ 3 positive ALNs), instead of metastasis or non-metastasis.We aimed to develop a radiomics nomogram integrating clinicopathologic features, ABUS imaging features and radiomics features from ABUS for predicting ALN tumor burden in early breast cancer.MethodsA total of 310 patients with breast cancer were enrolled. Radiomics score was generated from the ABUS images. Multivariate logistic regression analysis was used to develop the predicting model, we incorporated the radiomics score, ABUS imaging features and clinicopathologic features, and this was presented with a radiomics nomogram. Besides, we separately constructed an ABUS model to analyze the performance of ABUS imaging features in predicting ALN tumor burden. The performance of the models was assessed through discrimination, calibration curve, and decision curve.ResultsThe radiomics score, which consisted of 13 selected features, showed moderate discriminative ability (AUC 0.794 and 0.789 in the training and test sets). The ABUS model, comprising diameter, hyperechoic halo, and retraction phenomenon, showed moderate predictive ability (AUC 0.772 and 0.736 in the training and test sets). The ABUS radiomics nomogram, integrating radiomics score with retraction phenomenon and US-reported ALN status, showed an accurate agreement between ALN tumor burden and pathological verification (AUC 0.876 and 0.851 in the training and test sets). The decision curves showed that ABUS radiomics nomogram was clinically useful and more excellent than US-reported ALN status by experienced radiologists.ConclusionsThe ABUS radiomics nomogram, with non-invasive, individualized and precise assessment, may assist clinicians to determine the optimal treatment strategy and avoid overtreatment.

Predictors and Prognostic Significance of Postoperative Complications for Patients with Intrahepatic Cholangiocarcinoma.

The prognostic impact of major postoperative complications (POCs) for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. We sought to analyze the relationship between POCs and outcomes relative to lymph node metastases (LNM) and tumor burden score (TBS). Patients who underwent resection of ICC between 1990-2020 were included from an international database. POCs were defined according to Clavien-Dindo classification ≥ 3. The prognostic impact of POCs was estimated relative to TBS categories (i.e., high and low) and lymph node status (i.e., N0 or N1). Among 553 patients who underwent curative-intent resection for ICC, 128 (23.1%) individuals experienced POCs. Low TBS/N0 patients who experienced POCs presented with a higher risk of recurrence and death (3-year cumulative recurrence rate; POCs: 74.8% vs. no POCs: 43.5%, p = 0.006; 5-year overall survival [OS], POCs 37.8% vs. no POCs 65.8%, p = 0.003), while POCs were not associated with worse outcomes among high TBS and/or N1 patients. The Cox regression analysis confirmed that POCs were significant predictors of poor outcomes in low TBS/N0 patients (OS, hazard ratio [HR] 2.91, 95%CI 1.45-5.82, p = 0.003; recurrence free survival [RFS], HR 2.42, 95%CI 1.28-4.56, p = 0.007). Among low TBS/N0 patients, POCs were associated with early recurrence (within 2years) (Odds ratio [OR] 2.79 95%CI 1.13-6.93, p = 0.03) and extrahepatic recurrence (OR 3.13, 95%CI 1.14-8.54, p = 0.03), in contrast to patients with high TBS and/or nodal disease. POCs were independent, negative prognostic determinants for both OS and RFS among low TBS/N0 patients. Perioperative strategies that minimize the risk of POCs are critical to improving prognosis, especially among patients harboring favorable clinicopathologic features.

Characterization of lymph node metastases in prostate cancer.

380 Background: Unlike lymph node (LN) staging in other malignancies, prostate cancer nodal staging does not characterize or quantify the LN tumor burden. Detailed characterization of LN metastases may provide improved prognostic information, which could assist in post-surgical management decisions. Methods: Clinical and pathologic information was retrospectively collected via electronic medical record from 66 patients with pathologically confirmed LN involvement after radical prostatectomy with pelvic lymph node dissection performed by a single surgeon. Tissue slides of all positive LNs were re-evaluated by a single pathologist in accordance with our institutional review board protocol. Poisson regression analyses and Cox proportional-hazard regression were performed to evaluate the association of risk factors with the number of positive nodes and the association of LN characteristics with biochemical recurrence (BCR)-free survival. Results: Median number of positive LNs per patient was 2 (IQR 1-3). Mean % positive LNs per patient was 8.9 (SD10.4). Mean cumulative size of all tumor deposits in all positive LNs per patient was 5.0mm (SD 4.8). Average % surface area of LN involved by tumor was 28%. 48 (73%) patients were alive without disease at median follow-up time of 38 months (IQR 26-50 months). Higher pre-surgery PSA, clinical stage T3-T4 versus T1-2, extraprostatic extension (EPE), seminal vesical involvement (SVI), and lymphovascular invasion (LVI) were significantly associated with higher incidence rate of nodal positivity. Larger mean size of largest LN deposits, mean size of total LN deposits, and mean % surface area of LN involved were significantly associated with worse BCR-free survival. There was no significant association for number of positive nodes, LN anatomical compartments, extranodal extension (ENE), span of ENE, and distance of ENE from LN capsule. Higher pre-surgery PSA and post-surgery Gleason grade were significantly associated with worse BCR-free survival. Conclusions: Our data shows that LN tumor burden is associated with worse BCR-free survival. Anatomical LN compartments and quantification of ENE did not show significant association with BCR. [Table: see text]

Regional radiotherapy after primary systemic treatment for cN+ breast cancer patients

Pathologic complete response (pCR) after Primary Systemic Treatment (PST) for breast cancer is associated with excellent long-term outcomes. With increasing use of PST, the indication for regional nodal irradiation (RNI) has been challenged. The aim of this paper is to review the literature on de-escalation of RNI in patients treated with PST.We found no level 1 evidence on de-escalation of RNI after PST, but several randomized trials are ongoing. Consequently, current de-escalation strategies are based on cohort studies. These studies showed that in patients with low nodal tumour burden (LNTB) (≤3 suspicious nodes at imaging) prior to PST, and ypN0 based on Axillary Lymph Node Dissection (ALND), omission of RNI resulted in very low regional recurrences (RR) without compromising survival. In patients with LNTB and ypN0 based on Sentinel Lymph Node Biopsy (SLNB), omission of axillary treatment also resulted in low RR; the majority of these patients received local radiotherapy. Similarly, in patients with ypN1 (ALND) disease, omission of RNI resulted in low 5-year RR rates. Low RR-rates were also found in the few studies replacing ALND by RNI, in patients with ypN1 (SLNB) disease.In patients with high nodal tumour burden prior to PST and ypN0 (SLNB), replacing ALND by RNI also resulted in low RR. Due to the limited number of patients, these data should be interpreted with caution.We conclude that although level 1 evidence is lacking, de-escalation of RNI after PST can be considered in selected cases.

Nodal tumor burden provides independent predictive value for biochemical recurrence in patients with node-positive prostate cancer after definitive surgery

Nodal tumor burden provides independent predictive value for biochemical recurrence in patients with node-positive prostate cancer after definitive surgery

Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer.

Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient's clinical management.

Molecular Detection of Lymph Node Metastases in Lung Cancer Patients Using the One-Step Nucleic Acid Amplification Method:Clinical Significance and Prognostic Value.

The one-step nucleic acid amplification (OSNA) method allows for the quantitative evaluation of the tumor burden in resected lymph nodes (LNs) in patients with lung cancer. This technique enables to detect macro and micrometastases, facilitating the correct classification of patients for appropriate follow-up of the disease after surgery. Of 160 patients with resectable lung cancer whose LNs were examined by OSNA, H&E and CK19 IHC between July 2015 and December 2018, 110 patients with clinical stages from IA1 to IIIB were selected for follow-up. LN staging in lung cancer by pathological study led to understaging in 13.64% of the cases studied. OSNA allowed to quantify the tumor burden and establish a prognostic value. Patients with a total tumor load of ≥1650 cCP/uL were associated with a significantly increased likelihood of recurrence. Moreover, the survival of patients with <4405 cCP/uL was significantly higher than patients with ≥4405 cCP/uL. The OSNA assay is a rapid and accurate technique for quantifying the tumor burden in the LNs of lung cancer patients and OSNA quantitative data could allow to establish prognostic values for recurrence-free survival and overall survival in this type of malignancy.

Sentinel lymph node biopsy in extramammary Paget disease: A 13-year institutional experience.

Whether sentinel lymph node biopsy status is a prognostic factor or effective in determining treatment strategies in extramammary Paget disease remains unclear. This study aimed to investigate the significance of sentinel lymph node biopsy in extramammary Paget disease. We retrospectively reviewed the clinical information of previously untreated patients with invasive extramammary Paget disease who underwent wide local excision of the primary tumor and sentinel lymph node biopsy at our hospital between April 2008 and March 2021. Clinical data including the baseline neutrophil-to-lymphocyte ratio and recurrence-free survival were analyzed. Sentinel lymph node metastases were classified as macrometastases and micrometastases, with a cut-off value for sentinel lymph node tumor burden of 2 mm. Univariate and multivariate analyses of factors affecting sentinel lymph node biopsy positivity and recurrence-free survival rates were performed. Overall, 85 patients were included in the analysis. Patients in the sentinel lymph node biopsy-positive group (n=26) had a significantly higher invasion level and neutrophil-to-lymphocyte ratio. According to multivariate analyses, invasion level and a high neutrophil-to-lymphocyte ratio were independent predictive factors for sentinel lymph node biopsy positivity, and the sentinel lymph node biopsy status was an independent prognostic factor for recurrence-free survival. In conclusion, sentinel lymph node biopsy provides an accurate risk classification and clinical indication for postoperative follow-up in patients with invasive extramammary Paget disease.

Nomogram models for stratified prediction of axillary lymph node metastasis in breast cancer patients (cN0).

ObjectivesTo determine the predictors of axillary lymph node metastasis (ALNM), two nomogram models were constructed to accurately predict the status of axillary lymph nodes (ALNs), mainly high nodal tumour burden (HNTB, > 2 positive lymph nodes), low nodal tumour burden (LNTB, 1-2 positive lymph nodes) and negative ALNM (N0). Accordingly, more appropriate treatment strategies for breast cancer patients without clinical ALNM (cN0) could be selected.MethodsFrom 2010 to 2015, a total of 6314 patients with invasive breast cancer (cN0) were diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and internal validation groups at a ratio of 3:1. As the external validation group, data from 503 breast cancer patients (cN0) who underwent axillary lymph node dissection (ALND) at the Second Affiliated Hospital of Chongqing Medical University between January 2011 and December 2020 were collected. The predictive factors determined by univariate and multivariate logistic regression analyses were used to construct the nomograms. Receiver operating characteristic (ROC) curves and calibration plots were used to assess the prediction models’ discrimination and calibration.ResultsUnivariate analysis and multivariate logistic regression analyses showed that tumour size, primary site, molecular subtype and grade were independent predictors of both ALNM and HNTB. Moreover, histologic type and age were independent predictors of ALNM and HNTB, respectively. Integrating these independent predictors, two nomograms were successfully developed to accurately predict the status of ALN. For nomogram 1 (prediction of ALNM), the areas under the receiver operating characteristic (ROC) curve in the training, internal validation and external validation groups were 0.715, 0.688 and 0.876, respectively. For nomogram 2 (prediction of HNTB), the areas under the ROC curve in the training, internal validation and external validation groups were 0.842, 0.823 and 0.862. The above results showed a satisfactory performance.ConclusionWe established two nomogram models to predict the status of ALNs (N0, 1-2 positive ALNs or >2 positive ALNs) for breast cancer patients (cN0). They were well verified in further internal and external groups. The nomograms can help doctors make more accurate treatment plans, and avoid unnecessary surgical trauma.

Identification of the lymph node metastasis-related automated breast volume scanning features for predicting axillary lymph node tumor burden of invasive breast cancer via a clinical prediction model.

Breast cancer has become the malignant tumor with the highest incidence in women. Axillary lymph node dissection (ALND) is an effective method of maintaining regional control; however, it is associated with a significant risk of complications. Meanwhile, whether the patients need ALND or not is according to sentinel lymph node biopsy (SLNB). However, the false-negative results of SLNB had been reported. Automated breast volume scanning (ABVS) is a routine examination in breast cancer. A real-world cohort consisting of 245 breast cancer patients who underwent ABVS examination were enrolled, including 251 tumor lesions. The ABVS manifestations were analyzed with the SLNB results, and the ALND results for selecting the lymph node metastasis were related to ABVS features. Finally, a nomogram was used to construct a breast cancer axillary lymph node tumor burden prediction model. Breast cancer patients with a molecular subtype of luminal B type, a maximum lesion diameter of ≥5 cm, tumor invasion of the Cooper’s ligament, and tumor invasion of the nipple had heavy lymph node tumor burden. Molecular classification, tumor size, and Cooper’s ligament status were used to construct a clinical prediction model of axillary lymph node tumor burden. The consistency indexes (or AUC) of the training cohort and the validation cohort were 0.743 and 0.711, respectively, which was close to SLNB (0.768). The best cutoff value of the ABVS nomogram was 81.146 points. After combination with ABVS features and SLNB, the AUC of the prediction model was 0.889, and the best cutoff value was 178.965 points. The calibration curve showed that the constructed nomogram clinical prediction model and the real results were highly consistent. The clinical prediction model constructed using molecular classification, tumor size, and Cooper’s ligament status can effectively predict the probability of heavy axillary lymph node tumor burden, which can be the significant supplement to the SLNB. Therefore, this model may be used for individual decision-making in the diagnosis and treatments of breast cancer.

Ultrasound-guided radar reflector localization of axillary lymph nodes facilitates targeted axillary dissection

PurposeThis study evaluated feasibility and patient outcomes for targeted axillary lymph node (LN) dissection (TAD) with SAVI SCOUT® ultrasound-guided radar reflector localization (RRL). MethodsIn this IRB-approved retrospective study, 800 consecutive patients who underwent ultrasound-guided RRL between November 2017 and June 2020 were reviewed. Of these patients, those with axillary LN RRL were included in this study. Reports in the electronic medical record were reviewed to determine RRL placement, retrieval, and surgical outcomes. ResultsA total of 147 patients met inclusion criteria. Of these, axillary RRL was performed for biopsy-proven metastatic disease in 134 and inconclusive or benign biopsy in 13. RRL was successful in 146/151 lymph nodes (97%). Two patients had placement >10 mm from target and 3 had no post-placement signal. In all 5, the targets were successfully retrieved at surgery. Specimen radiographs were performed in 135 cases and confirmed the intended target in all 135 (100%). In 109 patients who underwent TAD + sentinel lymph node biopsy (SLNB), the RRL LN and the SLN(s) were different in 18 (17%). In 3 of these, the RRL LN was the only malignant LN (3%). In the 105 patients who underwent neoadjuvant chemotherapy, 43% (45/105) achieved nodal pCR and 85% (89/105) had <3 metastatic lymph nodes at surgery. ConclusionUltrasound-guided RRL of axillary LNs is a feasible approach to facilitate TAD with high placement and retrieval success rates. This enables TAD as an alternative to complete axillary LN dissection (cALND), sparing some patients with low nodal tumor burden from cALND.

SO-10 The prognostic role of microarchitecture in tumour-positive lymph nodes in oesophageal cancer patients: Results from the UK MRC OE02 trial

Patients with resectable oesophageal cancer (OeC) have a 25-47% 5-year overall survival (OS). The strongest prognostic factor is pathological lymph node (LN) status. Regional tumour-draining LNs play an important role in the host anti-tumour immune response. We previously demonstrated that the microarchitecture in tumour-negative LNs (LNneg) changes after chemotherapy and predicts OS. It is currently unknown whether neoadjuvant chemotherapy induces microarchitectural changes in regional tumour-positive LNs (LNpos) which might impact patient's OS. We hypothesized that (1) LNpos in OeC patients treated with chemotherapy and surgery contain fewer germinal centres compared to patients treated by surgery alone and (2) that patients with an activated anti-tumour immune response (e.g. more germinal centres and more lymphocytes) in the regional LNpos have a better OS. Digitized haematoxylin/eosin-stained sections of 129 OE02 trial patients with at least one LNpos were analyzed (70 treated with surgery alone (S patients), 59 treated with chemotherapy and surgery (CS patients)). The area of the different histological components (lymphocytes, germinal centres, histiocytes, tumour tissue) of the largest LNpos per patient was manually quantified by point counting as surrogate of LNpos microarchitecture. The %area of individual immune features in the tumour-free LN area and %area of tumour were calculated. The relationship between individual histological LN components, largest LNpos diameter, treatment and clinicopathological variables was analyzed. Kaplan Meier method was applied for univariate OS from time of surgery and Cox proportional hazard model for multivariate survival analysis including (y)pT status in the model. There was no difference in LNpos microarchitecture between treatment arms. Combined analysis showed that tumour tissue occupied (median(range)) 8.9% of the largest LNpos area (0.01-44.4%). Lymphocytes occupied most of the tumour-free LNpos area (median (range) 65.2% LN area (2.1%-87.7%), followed by histiocytes (9.7% LN area (0%-59.3%)) and germinal centres (1.8% LN area (0%-16.9%)). No relationship between individual LNpos components and clinicopathological parameters was found. S patients with a high %area of histiocytes in the LNpos had a poorer survival in univariate (p=0.008; HR 1.05 95% CI (1.01-1.09)) and in multivariate analysis (p=0.04; HR 1.06 (1.02-1.09)). CS patients with a larger area of tumour in the LNpos showed decreased OS in univariate (p=0.04; HR 2.27 (1.29-3.99)) and in multivariate analysis (p=0.01; HR 2.11 (1.19-3.75). No other relationships with survival were seen. This is the first study to quantify LNpos microarchitecture on haematoxylin/eosin-stained sections and show that LNpos microarchitecture is similar between oesophageal cancer patients treated with chemotherapy and surgery or surgery alone. This might indicate that chemotherapy does not alter the quantitative immune response in tumour-positive lymph nodes of oesophageal cancer patients. Nevertheless, there are differences in prognostic value of histiocytes in tumour-positive lymph nodes in surgery alone patients and residual tumor burden in tumour-positive lymph nodes in chemotherapy patients. The underlying molecular mechanisms of these novel findings warrant further investigations by for example detailed immune-cell phenotyping within lymph nodes and matched primary tumour. Our results need to be confirmed in a second independent series to translate findings into post-surgery patient treatment decisions in the future.

Outcomes in patients with resected stage IIIA melanoma treated with adjuvant nivolumab or monitored with observation: A real-world study.

e21534 Background: Nivolumab is approved in the United States and other countries as an adjuvant treatment for patients with completely resected stage III–IV melanoma based on results of the phase 3 CheckMate 238 trial, though the trial enrolled a limited number of patients with stage IIIA disease (AJCC-8). The objective of this real-world study is to describe characteristics, treatment patterns, and outcomes of patients with resected stage IIIA melanoma (AJCC-8) treated with adjuvant nivolumab or monitored with observation. Methods: In this retrospective, chart-review study, physicians from Cardinal Health’s proprietary Oncology Provider Extended Network (OPEN) extracted data from electronic health records of patients who had undergone complete surgical resection of stage IIIA melanoma between Jan. 1, 2018, and Dec. 31, 2019. Recurrence-free survival (RFS) and overall survival (OS) were evaluated from the date of resection and compared between the adjuvant nivolumab and observation cohorts using log-rank tests and adjusted Cox proportional hazards models (covariates included age, sex, race, region, payer type, ECOG PS, and Charlson Comorbidity Index). Discontinuations and deaths due to adjuvant nivolumab toxicity were assessed. Results: This study included 171 patients treated with adjuvant nivolumab and 38 patients monitored with observation. In the adjuvant nivolumab and observation cohorts, respectively, mean age was 57.4 and 68.1 years; most patients were male (59% and 68%) and white (90% and 87%); and median follow-up from resection was 20.7 and 25.0 months. Sentinel lymph node tumor burden of &lt; 1 mm was reported in 12% (n = 20) and 16% (n = 6) of patients in the adjuvant nivolumab and observation cohorts, respectively. The scheduled treatment course with adjuvant nivolumab was completed by 91% of patients (n = 155). RFS and OS rates were numerically higher with adjuvant nivolumab than with observation (Table). There was a trend toward RFS and OS benefit with adjuvant nivolumab versus observation (unadjusted RFS HR 0.53, 95% CI 0.26–1.09; adjusted RFS HR 0.62, 95% CI 0.28–1.40; unadjusted OS HR 0.55, 95% CI 0.19–1.57; adjusted OS HR 0.81, 95% CI 0.25–2.61). Discontinuation of adjuvant nivolumab due to toxicity occurred in 2% of patients (n = 4); no treatment-related deaths were reported. Conclusions: These real-world results confirm that patients with resected stage IIIA melanoma (AJCC-8) have a good prognosis. Treatment with adjuvant nivolumab may provide modest survival benefit over observation in this population, though increased sample size and additional follow-up are warranted.[Table: see text]