A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Prognostic Importance of Axillary Lymph Node Response to Neoadjuvant Systemic Therapy on Axillary Surgery in Breast Cancer-A Single Center Experience.

Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2- early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2-, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6-20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases.

Frequency of axillary nodal complete pathological response of breast cancer patients in neoadjuvant chemotherapy setting: A cross-sectional study.

Objectives: Pathological complete response (pCR) occurs in about 20-30% of patients undergoing systemic neoadjuvant therapy. This leads to the idea of sparing the patient the morbidity associated with axillary surgery. "Wait and watch" policy for cancers which achieve complete pathological response on neoadjuvant systemic therapy is a well-established practice in various cancers like the esophagus, rectum and larynx. This has led to organ preservation protocols being practiced worldwide for these cancers without affecting the overall survival of the patient. We believe patients undergoing a complete pathological response in the breast may be spared axillary surgery. Axillary surgery leads to morbidity and extra financial burden with no added advantage in survival. Material and Methods: A total of 326 patients with breast cancer who had received neoadjuvant systemic chemotherapy from 2015 to 2020 were included in our retrospective study. Final histopathology of the breast and axillary surgery was noted to report the frequency of complete pathological response. The frequency of positive nodal disease with respect to stage, grade and type of cancer was measured. Results: Among 326 patients, our study showed that 53% of patients with complete pathological response in breast also had complete response in the axilla compared to 43% with incomplete pathological response. No significant difference was found for age, menopausal status, initial tumor size when patients with complete pathological response were compared to non or partial responders. The rate of complete pathological response was higher in patients with clinically node negative patients after NACT, hormone negative, HER2 positive and triple negative population. Conclusion: Our results indicated that 53% of the patients who developed complete pathological response in the breast underwent needless axillary procedure. Axillary surgery can be staged after the breast surgery if residual tumor is present on the histopathological specimen. In case of pCR, omission of axillary surgery can be considered. However, a larger population, multi-centric studies are needed for treatment guidelines.

Nodal response to primary systemic therapy predicts prognosis of cN3c breast cancer patients receiving multimodality therapy.

AIM: To investigate the survival outcomes, patterns and risks of recurrence in cN3c breast cancer patients after multimodality therapy, as well as the predictors of candidates for ipsilateral supraclavicular (SCV) area boosting. METHOD: Consecutive cN3c breast cancer patients from January 2009 to December 2020 were retrospectively reviewed. Based on nodal response to primary systemic therapy (PST), patients were categorized into three groups: clinical complete response (cCR) not achieved in SCV lymph nodal (SCLN, Group A), SCLN cCR but axillary node (ALN) did not achieve pathological complete response (pCR, Group B), cCR in SCLN and pCR in ALN (Group C). RESULTS: The median follow-up time was 32.7 months. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64.6% and 43.7% respectively. Multivariate analysis showed cumulative SCV dose and ypT stage, ALN response and SCV response to PST were significantly associated with OS and RFS respectively. Compared with Group A or B, Group C showed significantly improved 3 y-RFS (53.8% vs 73.6% vs 100%, p = 0.003), and the lowest rate of DM as first failure (37.9% vs 23.5% vs 0%, p = 0.010). In Group A, the 3 y-OS for patients receiving the cumulative SCV dose of ≥60 Gy versus <60 Gy was 78.0% versus 57.3% (p = 0.029). CONCLUSION: Nodal response to PST is an independent prognostic factor for survival and pattern of failure. A cumulative SCV dose of ≥60 Gy is positively associated with improved OS, especially in Group A. Our data supports the perspective of optimizing radiotherapeutic strategy based on nodal response.

The great deceiver: a case series of 'double fire' atrioventricular nodal response.

Background: The 'double fire' (DF) atrioventricular (AV) nodal response is a rare mechanism of two ventricular electrical activations following a single atrial beat due to dual AV node physiology. DF AV nodal response is often misdiagnosed and may lead to unnecessary invasive procedures. Case summary: We describe a series of three cases with distinct clinical manifestations of DF AV nodal response: Patient 1 remained symptomatic after slow pathway modification for common AV nodal re-entry tachycardia. Patient 2 was misdiagnosed as having junctional bigeminy and developed heart failure with reduced left ventricle ejection fraction. Patient 3 was misdiagnosed as having atrial fibrillation (AF) and underwent two pulmonary vein isolation (PVI) procedures, without clinical improvement. All patients underwent an electrophysiological study (EPS) during which DF AV nodal response was confirmed and treated with radiofrequency ablation of the slow pathway. All patients were afterwards relieved from their symptoms. Discussion and conclusion: DF AV nodal response is a rare electrophysiological phenomenon which can be clinically misinterpreted as other common arrhythmias, such as premature junctional bigeminy or AF and can contribute to tachycardia induced cardiomyopathy. Typical electrocardiogram- and EPS-derived findings can be indicative for DF AV nodal response. DF AV nodal response can be easily and effectively treated by slow pathway ablation.

Para-Hisian pacing: The eyes see what the mind knows.

A young male presented with pre-excited atrial fibrillation. During an electrophysiology study, preexcitation suggestive of a pathway in posteroseptal location was confirmed but no tachycardia was inducible. Para-Hisian pacing was done during sinus rhythm. Is there retrograde conduction through the accessory pathway?

What Is the Response Seen During Para-Hisian Pacing?

We present an interesting tracing of para-Hisian pacing in a 45-year-old man with an episode of narrow complex tachycardia and past recurrent palpitations.

Radiomic Model Predicts Lymph Node Response to Induction Chemotherapy in Locally Advanced Head and Neck Cancer.

This study developed a pretreatment CT-based radiomic model of lymph node response to induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. This was a single-center retrospective study of patients with locally advanced HPV+ HNSCC. Forty-one enlarged lymph nodes were found from 27 patients on pretreatment CT and were split into 3:1 training and testing cohorts. Ninety-three radiomic features were extracted. A radiomic model and a combined radiomic-clinical model predicting lymph node response to induction chemotherapy were developed using multivariable logistic regression. Median age was 57 years old, and 93% of patients were male. Post-treatment evaluation was 32 days after treatment, with a median reduction in lymph node volume of 66%. A three-feature radiomic model (minimum, skewness, and low gray level run emphasis) and a combined radiomic-clinical model were developed. The combined model performed the best, with AUC = 0.85 on the training cohort and AUC = 0.75 on the testing cohort. A pretreatment CT-based lymph node radiomic signature combined with clinical parameters was able to predict nodal response to induction chemotherapy for patients with locally advanced HNSCC.

Prospective Feasibility Trial of Sentinel Lymph Node Biopsy in the Setting of Inflammatory Breast Cancer.

BACKGROUND: Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging. PATIENTS AND METHODS: Patients with IBC were prospectively enrolled. Patients underwent axillary staging with physical examination and axillary ultrasound before and after NACT. All patients underwent SLNB using blue dye and radioisotope, followed by ALND. RESULTS: Sixteen patients were prospectively enrolled. Clinical N stage was N0 in 1 patient, N1 in 8, and N3 in 7. SLN mapping was successful in only 4 patients (25%) with 12 (75%) not draining either tracer to a SLN. Three of the 4 (75%) who mapped had an axillary pCR. The patient who mapped but did not have an axillary pCR had a positive SLNB with additional axillary nodal disease identified on ALND. All patients who successfully mapped had presumed residual nodal disease on preoperative axillary ultrasound. CONCLUSION: SLNB was unsuccessful in most IBC patients. A small subset who have pCR might undergo successful SLNB, but preoperative axillary imaging failed to identify these patients. ALND should remain standard practice for IBC patients.

High nodal positivity rates even in good clinical responders after chemoradiation of rectal cancer: is organ preservation feasible?

AIM: Local excision (LE) is emerging as a treatment option for rectal cancer responding well to chemoradiation. However, it does not address the mesorectal nodal burden. We aimed to identify the factors influencing nodal positivity and subsequently defined a low-risk group by including only patients at low risk. METHOD: A single-centre, retrospective database analysis was carried out of patients with radically resected rectal cancer after neoadjuvant chemoradiation. RESULTS: This study included 524 patients with predominantly low rectal tumours. Nodal positivity among ypT0, T1 and T2 groups was 14.7%, 28% and 30%, respectively. Multivariate analysis with stepwise logistic regression identified the following low-risk features: age ≥ 40 years, nonsignet ring cell carcinoma (SRCC) histology and pathological complete response (pCR). Sixty-nine patients fulfilling all three criteria were analysed and the nodal positivity was found to be 10.1%, which implies that, if these patients had been selected for LE, one in 10 would have had positive mesorectal nodes. CONCLUSION: Even in patients with low-risk criteria (pCR, non-SRCC histology and age ≥ 40 years), the residual positive nodal disease burden is 10%. Whether this high incidence of residual nodal disease translates into a similar risk of locoregional recurrence if an organ-preservation strategy is adopted is unclear.

The role of postmastectomy radiotherapy in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB.

PURPOSE: The role of postmastectomy radiotherapy (PMRT) in clinically node-positive, stage II-III breast cancer patients with pathological negative nodes (ypN0) after neoadjuvant chemotherapy (NAC) remains controversial. METHODS: A total of 1560 clinically node-positive, stage II-III breast cancer patients treated with NAC and mastectomy who achieved ypN0 between 1998 and 2009 in the National Cancer Database were analyzed. The effects of PMRT on overall survival (OS) for the entire cohort and multiple subgroups were evaluated. Imputation and propensity score matching were used as sensitivity analyses to minimize biases. RESULTS: Of the entire 1560 eligible patients, 903 (57.9%) received PMRT and 657 (42.1%) didn't. At a median follow-up of 56.0 months, no statistical difference was observed for OS between two groups by univariate and multivariate analyses (P = 0.120; HR 1.571, 95% CI 0.839-2.943). On subgroup analyses, PMRT significantly improved OS in patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast cancer after NAC (P < 0.05). This improvement in OS remained significant after sensitivity analyses for the propensity score-matched patients. CONCLUSIONS: This study demonstrated that PMRT showed a heterogeneous effect in clinically node-positive, stage II-III breast cancer patients with ypN0 following NAC. PMRT improved OS for patients with clinical stage IIIB/IIIC disease, T3/T4 tumor, or residual invasive breast tumor after NAC. In the absence of definitive conclusions from prospective studies, including the ongoing NSABP B-51 trial, our findings may help identify specific groups of women with clinically node-positive, stage II-III breast cancers who could benefit from PMRT after NAC.