Sentinel Lymph Node Detection in Cutaneous Melanoma Using Indocyanine Green-Based Near-Infrared Fluorescence Imaging: A Systematic Review and Meta-Analysis.

The standard of care approach to identify sentinel lymph nodes (SLNs) in clinically non-metastatic cutaneous melanoma patients is technetium (Tc)-based lymphoscintigraphy. This technique is associated with radiation exposure, a long intervention time, high costs, and limited availability. Indocyanine green (ICG)-based near-infrared fluorescence imaging offers a potential alternative if proven to be of comparable diagnostic accuracy. While several clinical cohorts have compared these modalities, no systematic review exists that provides a quantitative analysis of their results. Hence, a systematic literature review was conducted in December 2023 considering clinical studies comparing the diagnostic accuracy of ICG and Tc for sentinel lymph node biopsy in cutaneous melanoma patients. Three hundred nineteen studies were identified and further screened in accordance with the PRISMA 2020 guidelines, resulting in seven studies being included in the final meta-analysis. Tc identified a significantly higher number of SLNs and metastatic SLNs in prospective studies only. However, in the overall meta-analysis of all included comparative studies, no significant differences were found regarding the identification of metastatic patients or the false negative rate (FNR). ICG may be a non-inferior alternative to Tc for intraoperative guidance in sentinel lymph node biopsy in cutaneous melanoma patients. Future randomized controlled trials are needed, especially regarding the preoperative, transcutaneous identification of the affected lymph node basin.

Melanoma-Derived Extracellular Vesicles Induce CD36-Mediated Pre-Metastatic Niche.

CD36 expression in both immune and non-immune cells is known to be directly involved in cancer metastasis. Extracellular vesicles (EVs) secreted by malignant melanocytes play a vital role in developing tumor-promoting microenvironments, but it is unclear whether this is mediated through CD36. To understand the role of CD36 in melanoma, we first analyzed the SKCM dataset for clinical prognosis, evaluated the percentage of CD36 in lymphatic fluid-derived EVs (LEVs), and tested whether melanoma-derived EVs increase CD36 expression and induce M2-macrophage-like characteristics. Furthermore, we performed a multiplex immunofluorescence (MxIF) imaging analysis to evaluate the CD36 expression and its colocalization with various other cells in the lymph node (LN) of patients and control subjects. Our findings show that cutaneous melanoma patients have a worse clinical prognosis with high CD36 levels, and a higher percentage of CD36 in total LEVs were found at baseline in melanoma patients compared to control. We also found that monocytic and endothelial cells treated with melanoma EVs expressed more CD36 than untreated cells. Furthermore, melanoma-derived EVs can regulate immunosuppressive macrophage-like characteristics by upregulating CD36. The spatial imaging data show that cells in tumor-involved sentinel LNs exhibit a higher probability of CD36 expression than cells from control LNs, but this was not statistically significant. Conclusively, our findings demonstrated that CD36 plays a vital role in controlling the immunosuppressive microenvironment in the LN, which can promote the formation of a protumorigenic niche.

Risk Factors for Non-sentinel Lymph Node Metastasis in HR+/HER2- Breast Cancer With cN0.

BACKGROUND/AIM: This study aimed to identify the risk factors associated with non-sentinel lymph node (non-SLN) metastasis in case of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with cN0 on preoperative exam, where the sentinel lymph node (SLN) is positive. PATIENTS AND METHODS: We conducted a retrospective review of medical records from the Chonnam National University Hwasun Hospital, spanning from January 2013 to January 2020, focusing on patients with HR+, HER2- breast cancer. Specifically, we collected the clinical and pathological data for those patients who underwent axillary lymph node dissection (ALND) due to positive SLN. RESULTS: Among the 166 patients who underwent ALND after positive SLNs, median patient age was 52 years. Univariate analyses demonstrated a significant association between non-SLN metastasis and the number of positive SLNs (p=0.039), SLN positive ratio (p<0.001), and primary tumor size (p=0.018). Multivariate analysis revealed that an SLN ratio >0.55 (p=0.004, HR=3.007, 95% CI=1.427-6.335) was independently associated with non-SLN metastasis. However, neither the number of positive SLN nor primary tumor size showed associations with non-SLN metastases. CONCLUSION: In patients with HR+, HER2- breast cancer who are cN0, completion of ALND should be considered when the positive SLN ratio is ≥0.55. This approach aims to provide the opportunity for survival benefit through additional adjuvant therapy or to contribute to de-escalation of unnecessary surgery.

Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.

BACKGROUND: Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year. OBJECTIVES: This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up. MATERIALS AND METHODS: This is a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples. RESULTS: Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes. This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients. CONCLUSIONS: Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.

Mexican consensus about surgical treatment in early-stage cervicouterine cancer.

Introduction: Cervical cancer is a public health problem in our country and worldwide. Less than 25% of cases are diagnosed in the early stages, where survival is more remarkable than 90% at five years. Here, we review surgical treatment in the early stages of cervical cancer. Methodology: A literature review was carried out in the MEDLINE database. The search was mainly limited to the English language, with priority given to systematic reviews with or without meta-analysis and randomized studies. However, only retrospective or observational evidence was found for some topics. Results: The standard treatment for early-stage cervical cancer is hysterectomy, and its radical nature will depend on the tumor size, lymphovascular permeation, and tumor-specific prognostic factors. Furthermore, the type of surgery (hysterectomy or trachelectomy) will rely on the patient's desire to preserve fertility. Nodal evaluation is indicated as part of the treatment from stage IAI with PLV. However, the sentinel lymph node is more relevant in the treatment. The incidental finding of cervical cancer after a hysterectomy requires a multidisciplinary evaluation to determine the therapeutic approach. Less radical surgery has been described as oncologically safe in low-risk groups. Conclusion: Surgical treatment in its early stages has evolved in recent decades, making it more individualized and seeking less morbidity in patients without compromising their survival.

Tubular Carcinoma of the Breast: The Possibility to Omit Sentinel Lymph Node Biopsy.

Background/Aim: Tubular breast carcinoma, classified as a special type of invasive cancer, has a good prognosis. This study aimed to retrospectively investigate the clinical and pathological characteristics of 32 tubular carcinoma cases enrolled at our institution, with a focus on exploring the potential for treatment de-escalation. Patients and Methods: The study included all patients diagnosed with tubular breast carcinoma at our hospital between January 2005 and December 2021. In addition, 549 patients with ductal carcinoma in situ (DCIS) and 1,524 patients with stage I and II invasive cancers [not otherwise specified (NOS)] were selected for comparison. Results: All participants were female, with an average age of 54.4 years. The median follow-up duration was 64 months. The median tumor diameter was 7 mm, and all cases were Luminal A type. Moreover, no lymph vascular invasion was observed in any case, and no local recurrence, distant metastasis, or death occurred. The sentinel lymph node positive rate was 0% in the tubular carcinoma group, significantly lower than that in the NOS group (25.5%, p=0.0019) and not significantly different from that in the DCIS group (0.2%). The tubular carcinoma group tended to have better overall survival (OS) and disease-free survival (DFS) than the NOS group. Furthermore, the tubular carcinoma group was not inferior in OS and DFS compared to the DCIS group. Conclusion: Lymph node metastasis rate, OS, and DFS of the tubular carcinoma group are comparable to those of the DCIS group. Sentinel lymph node biopsy for tubular carcinoma can be omitted with an accurate preoperative diagnosis.

Surgical nodal assessment for endometrial hyperplasia - A meta-analysis and systematic review.

OBJECTIVE: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. METHODS: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). RESULTS: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. CONCLUSIONS: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy.

Prediction of the number of positive axillary lymph nodes according to sentinel lymph node involvement and biological subtypes in patients receiving neoadjuvant chemotherapy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for assessing axillary lymph node status in clinically node-negative breast cancer patients. However, the approach to axillary surgery after neoadjuvant treatment is still controversial. In the present study, our objective was to predict the pathological nodal stage based on SLNB results and the clinicopathological characteristics of patients who initially presented with clinical N1 positivity but whose disease status was converted to clinical N0 after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: After NAC, 150 clinically node-negative patients were included. The relationships between clinicopathologic parameters and the number of positive lymph nodes in SLNBs and ALNDs were assessed through binary/multivariate logistic regression analysis. RESULTS: Among 150 patients, 78 patients had negative SLNBs, and 72 patients had positive SLNBs. According to the ALND data of 21 patients with SLNB1+, there was no additional node involvement (80.8%), 1-2 lymph nodes were positive in 5 patients (19.2%), and no patient had ≥ 3 lymph nodes involved. Following the detection of SLNB1 + positivity, the rate of negative non-sentinel nodes were 75% in the luminal A/B subgroup, 100% in the HER-2-positive subgroup, and 100% in the triple-negative subgroup. Patients with a lower T stage (T1-3 vs. T4), fewer than 4 clinical nodes before NAC (< 4 vs. ≥4), and a decreased postoperative Ki-67 index (< 10% vs. stable/increase) were included. According to both univariate and multivariate analyses, being in the triple-negative or HER2-positive subgroup, compared to the luminal A/B subgroup (luminal A/B vs. HER2-positive/triple-negative), was found to be predictive of complete lymph node response. CONCLUSION: The number of SLNB-positive nodes, tumor-related parameters, and response to treatment may predict no additional nodes to be positive at ALND.

Lower limb lymphedema after surgical staging for endometrial cancer: Current insights and future directions.

Lower extremity lymphedema (LEL) is a common complication following surgical staging of endometrial cancer. LEL is a chronic condition associated with significant impact on patient morbidity and quality of life (QoL). This review aimed to report the current evidence in the literature on secondary LEL after surgical staging for endometrial cancer, focusing on the incidence based on different approaches to lymph node staging, diagnosis, risk factors, and the impact on QoL. Due to the absence of a standardized agreement regarding the methodology for evaluating LEL, the documented frequency of occurrence fluctuates across different studies, ranging from 0% to 50%. Systematic pelvic lymphadenectomy appears to be the primary determinant associated with the emergence of LEL, whereas the implementation of sentinel lymph node biopsy has notably diminished the occurrence of this lymphatic complication after endometrial cancer staging. LEL is strongly associated with decreased QoL, lower limb function, and negative body image, and has a detrimental impact on cancer-related distress reported by survivors. Standardization of lymphedema assessment is needed, along with cross-cultural adaptation of subjective outcome measures for self-reported LEL. The advent of sentinel lymph node mapping represents the ideal approach for accurate nodal assessment with less short- and long-term morbidity. Further research is needed to definitively assess the prevalence and risk factors of LEL and to identify strategies to improve limb function and QoL in cancer survivors with this chronic condition.

Transvaginal natural orifice transluminal endoscopic surgery (VNOTES) retroperitoneal sentinel lymph node BIOPSY compared with conventional laparoscopy in patients with endometrial cancer.

INTRODUCTION: To explore the possibility of treatment with VNOTES sentinel lymph node dissection concept in patients with endometrial cancer. METHODS: Patients who underwent VNOTES sentinel lymph node biopsy with the Comba modification were compared to patients who underwent conventional laparoscopic sentinel lymph node biopsy performed by the same surgical team. A total of 38 patients who underwent sentinel lymph node biopsy + total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (BSO) were compared with 19 patients who underwent VNOTES retroperitoneal sentinel lymph node biopsy + hysterectomy and BSO. Surgical steps were described. RESULTS: The average operation time, perioperative blood loss, the number of sentinel lymph nodes, presence of complications, and preoperative-postoperative hemoglobin-hematocrit differences, tumor stages, grades, largest tumor diameter, depths of invasion, and histological subtypes were similar in both the VNOTES and conventional laparoscopy groups. The postoperative pain scores were lower and the hospital stay was shorter in the VNOTES group than in the conventional laparoscopy group. No disease recurrence had been detected in either group at the time of writing. CONCLUSION: Compared to conventional laparoscopy, sentinel lymph node biopsy with the VNOTES technique provides similar surgical results and is more advantageous in terms of postoperative pain and hospital length of stay.

Intraoperative diagnosis of breast cancer metastasis in axillary lymph nodes: Cytological Smear vs. Frozen Section.

BACKGROUND: Intraoperative evaluation of axillary lymph nodes is sometimes required to determine the extent of surgery. In this study, we wished to assess the reliability of cytologic smear (CS) in determining lymph node involvement with tumor. Theoretically, CS provides more substance for examination than touch-imprint cytology and is faster to perform than frozen section (FS). We hypothesized that CS sensitivity for tumor cell detection in the lymph nodes would be similar to FS, at least 0.90. METHODS: This was a retrospective observational study at the Rambam Health Care Campus (January, 2013-June, 2020). Lymph nodes underwent intraoperative evaluation using either CS or FS, based on the availability of a cytologist at the time of the examination. Both intraoperative evaluations were compared to the final pathology following fixation with formalin. RESULTS: Eighty-eight patients undergoing intraoperative analysis were analyzed (51 CS, 37 FS). False-negative tests were recorded in only 1 patient evaluated by each of the 2 methods. This resulted in sensitivity 0.91 (95%CI 0.59, 1.00) for CS and 0.88 (95%CI 0.47, 1.00) for FS, specificity 1.00 (95%CI 0.91, 1.00) for CS and 1.00 (95%CI 0.88, 1.00) for FS, positive predictive value 1.00 (95%CI 0.69, 1.00) for CS and 1.00 (95%CI 0.59, 1.00) for FS, and negative predictive value 0.98 (95%CI 0.87, 1.00) for CS and 0.97 (95%CI 0.83, 1.00) for FS. CONCLUSIONS: The sensitivity of the CS in this study is comparable to that of FS and due to shorter analysis time required is the preferred method at our institution.

Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound.

BACKGROUND: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. METHODS: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. RESULTS: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1-12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). CONCLUSIONS: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

[Own experience of indocyanine green use in the diagnosis and treatment of breast cancer in N.N. Petrov NMRC of Oncology]. / Sobstvennyi opyt ispol'zovaniya indotsianina zelenogo v diagnostike i lechenii raka molochnoi zhelezy v NMITs onkologii im. N.N. Petrova.

OBJECTIVE: To evaluate the possibility of using the method of sentinel lymph nodes (SLN) detection with indocyanine green (ICG) in patients with early breast cancer and its informativeness. MATERIAL AND METHODS: A «Determination of sentinel lymph nodes by fluorescence method intraoperatively with the use of indocyanine green¼ study, in which 168 patients are currently included, is being conducted in the clinic of the N.N. Petrov NMRC of Oncology from 2017 through the present. All patients who underwent biopsy of sentinel lymph nodes (BSLN) were primary with a T1-2N0M0 stage of process. RESULTS: The average number of axillary lymph nodes removed in BSLN was 3 (1-5). Accumulation of ICG was found in 147 (88%) patients, accumulation of labeled radiocolloid - in 137 (82%), in combination of ICG/radiocolloid - in 167 (99%) based on the results of imaging. CONCLUSION: The obtained results prove that the informativeness and relative simplicity of this method use allow its application in any hospital where breast cancer is surgically treated, as well as in the absence of radioisotopic equipment.

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. METHODS: Using the National Cancer Database (2010-2020), patients ≥ 70 years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. RESULTS: Of the 17,609 patients included, 94% underwent upfront surgery (n = 16,492) and the remaining underwent NAT (n = 1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. CONCLUSIONS: Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer.

BACKGROUND: The Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer. METHODS: The National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery. RESULTS: Of 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020. CONCLUSION: This study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.

The Utility of Sentinel Lymph Node Biopsy in Elderly Patients with Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is performed less often for older patients with melanoma. We investigated the association of SLNB and melanoma-specific survival (MSS) in the elderly. METHODS: We retrospectively reviewed the Surveillance, Epidemiology, and End Results (SEER: 2010-2019) for patients ≥ 70 years with cT2-4N0M0 melanoma. We used multivariable Cox proportional hazard models to evaluate the impact of SLNB performance and SLN status on MSS at increasing age cutoffs. In addition, we evaluated the association of different factors with SLNB performance using multivariable logistic regression. RESULTS: We identified 11,548 patients. Sentinel lymph node biopsy occurred in 6754 (58.5%) patients, 1050 (15.5%) of whom had a positive SLN. On adjusted SEER analysis, a negative SLN was independently associated with improved MSS (overall hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.63-0.67) for patients up to 87 years old. Positive SLNB was independently associated with inferior MSS (HR 1.71, 95% CI 1.93-1.98). Increasing age groups were significantly associated with decreased SLNB performance. CONCLUSIONS: Sentinel lymph node biopsy is associated with cancer-specific survival and adds prognostic information for elderly patients with melanoma. Sentinel lymph node biopsy performance should not be eliminated in elderly patients based on age alone, unless justified by poor performance status, patient preference, or other surgical contraindications. Decreased SLNB performance with increasing age in our cohort may indicate a missed therapeutic opportunity in the care of elderly patients with melanoma.

Clipping the Positive Lymph Node in Patients with Clinically Node Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: Impact on Axillary Surgery in the ISPY-2 Clinical Trial.

BACKGROUND: For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain. PATIENTS AND METHODS: We retrospectively analyzed cN+ ISPY-2 patients (2011-2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial. RESULTS: Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8-6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4-1.7, p = 0.7; HR 1.8, 95% CI 0.5-6.0, p = 0.3, respectively]. CONCLUSION: Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC.

The Incidence of Breast Cancer Lymph Node Involvement in Trinidad and Tobago.

Objective This study aims to investigate breast cancer lymph node involvement in a West Indian population while correlating it with various histological parameters and evaluating the role of the sentinel lymph node biopsy. Method This is a retrospective study where histology reports for all breast cancer-related biopsies from 2018 to 2021, totaling 813 samples, were obtained. Histological parameters from these reports were extracted into a spreadsheet and analyzed using Statistical Product and Service Solutions (SPSS, version 28.0; IBM SPSS Statistics for Windows, Armonk, NY) software for TNM staging and axillary and sentinel lymph node dissections, among other fields found in histology reports. Results In 44.8% of cases, patients present at the T2 stage with associated lymph node spread. Each T stage had more lymph nodes involved than uninvolved for tumors sized T2 and higher. Inversely, for tumors staged under T2, there were generally more uninvolved lymph nodes than involved ones. Larger tumors were found to have advanced N staging, especially in the T3 category, where a significantly higher proportion of cases were found to have N2 and N3 staging compared to the other T stages. This trend is also seen in M staging, where larger tumors metastasize more than smaller tumors (40% for T4a, 0% for T1). Despite significant lymph node involvement being observed, sentinel lymph node biopsies were usually negative. Conclusion More patients in this population present with lymph node involvement than without. Larger breast cancer tumors are associated with greater lymph node involvement, particularly at T2 and higher stages. Sentinel lymph node biopsies can be omitted in smaller breast cancer tumors up to 2 cm in size, and the local recurrence rate is low despite a false-negative rate of around 10% in upfront sentinel lymph node biopsy.

Preoperative prediction of nodal status using clinical data and artificial intelligence derived mammogram features enabling abstention of sentinel lymph node biopsy in breast cancer.

Introduction: Patients with clinically node-negative breast cancer have a negative sentinel lymph node status (pN0) in approximately 75% of cases and the necessity of routine surgical nodal staging by sentinel lymph node biopsy (SLNB) has been questioned. Previous prediction models for pN0 have included postoperative variables, thus defeating their purpose to spare patients non-beneficial axillary surgery. We aimed to develop a preoperative prediction model for pN0 and to evaluate the contribution of mammographic breast density and mammogram features derived by artificial intelligence for de-escalation of SLNB. Materials and methods: This retrospective cohort study included 755 women with primary breast cancer. Mammograms were analyzed by commercially available artificial intelligence and automated systems. The additional predictive value of features was evaluated using logistic regression models including preoperative clinical variables and radiological tumor size. The final model was internally validated using bootstrap and externally validated in a separate cohort. A nomogram for prediction of pN0 was developed. The correlation between pathological tumor size and the preoperative radiological tumor size was calculated. Results: Radiological tumor size was the strongest predictor of pN0 and included in a preoperative prediction model displaying an area under the curve of 0.68 (95% confidence interval: 0.63-0.72) in internal validation and 0.64 (95% confidence interval: 0.59-0.69) in external validation. Although the addition of mammographic features did not improve discrimination, the prediction model provided a 21% SLNB reduction rate when a false negative rate of 10% was accepted, reflecting the accepted false negative rate of SLNB. Conclusion: This study shows that the preoperatively available radiological tumor size might replace pathological tumor size as a key predictor in a preoperative prediction model for pN0. While the overall performance was not improved by mammographic features, one in five patients could be omitted from axillary surgery by applying the preoperative prediction model for nodal status. The nomogram visualizing the model could support preoperative patient-centered decision-making on the management of the axilla.