TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy.

BACKGROUND: While BRAF mutations seem important for early melanomagenesis, mutations in the TERT promoter (TERTp) are related to metastasis. Yet, in conventional melanoma management, risk stratification does not depend on molecular biomarkers that can indicate the stage of progression, but rather on clinical, pathological, sentinel lymph node (SLN), and radiologic evaluation. The aim of this work was to evaluate the frequency and prognostic impact of TERTp mutations, comparing their predictive value to those of conventional procedures in melanoma management. METHODS: Mutational analysis of a series of 91 cases was performed. The correlations between TERTp and BRAF mutational status and clinicopathological features were assessed. RESULTS: The mutation rate was 33% for TERTp and 30% for BRAF. There was 68% concordance between primary and metastatic samples for TERTp mutations and 92% for BRAF mutations. TERTp mutations are significantly associated with the presence of BRAF mutations, features of worse prognosis, and a reduced disease-free survival. Also, TERTp mutational status was similar to SLN biopsy as a predictive factor of cutaneous melanoma recurrence and metastasis. CONCLUSIONS: The predictive value of TERTp mutations may be similar to that of SLN biopsy and its integration in the management algorithm of melanoma patients should be considered.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

Sentinel lymph node (sln) in breast cancer. Review of current identification methods.

The subject of the paper is the review of the current methods for identifying the sentinel lymph node in breast cancer treatment, taking into account the latest techniques and based on the up-to-date analyses of many years of experience in using this method.

Nano-tracers for sentinel lymph node detection: current trends in technique and application.

Sentinel lymph node (SLN) detection and biopsy is a critical staging component for several cancers. Apart from established methods using dyes or radiolabeled colloids, newer techniques are emerging, like near-infrared fluorescent compounds, targeted molecular radiopharmaceuticals and magnetic nano-tracers. In the overview section of this review, we categorize SLN detection tracers based on their principle of use. We discuss the merits of existing tracers and provide a glimpse of in-development formulations. A subsequent clinical section explores the expanded role of SLN detection in management of various cancers, citing current medical guidelines and the leading conclusions of long-term clinical trials. The concluding section tries to provide a perspective of promising developments and the work required to bring them to clinical fruition.

A Prospective Cohort Study on Neck Lymph Node Mapping in Oral Cancers Using Methylene Blue Dye.

In the current scenario, the management of N0 neck in early-stage oral cancer is debatable, whether or not they should undergo elective neck dissection. Most of the time these patients are either over-treated or under-treated. Sentinel lymph node (SLN) biopsy is a good option to identify occult LN in this cohort of patients for guiding neck dissection. With a focus on SLN biopsy using methylene blue dye, this study aims to evaluate its feasibility and accuracy in node-negative oral squamous cell carcinoma. A prospective observational study was conducted involving operable squamous cell carcinoma patients with clinically and radiologically node-negative neck. Methylene blue was injected in the peritumoral area and after that SLN was identified and then neck dissection was completed. Of 47 patients, SLN was identified in 82.98%, with 53.85% having more than two SLN. Common locations were in levels IB, IA and IIA. Occult metastasis was observed in 12.82% of cases, predominantly in T2 patients. Sensitivity, specificity and NPV were 50%, 100% and 88.89% respectively. The study affirms the feasibility and accuracy of methylene blue-assisted SLN biopsy in oral cancer. Despite a high detection rate, methylene blue dye alone should not be used for SLN identification in oral cavity cancer. However, it can be used as an adjunct of lymphoscintigraphy to increase the yield of the procedure. Multi-institutional trials with larger cohorts may provide valuable insights and more information for comprehensively addressing the limitations of this technique and its broader applicability in decision-making, particularly in resource-constrained countries like India where lymphoscintigraphy is not readily accessible.

Staff radiation doses during Sentinel Lymph Node procedure of breast cancer from injection to surgeon.

The Sentinel Lymph Node (SLN) or Sentinel Lymph Node Biopsy (SLNB) technique involves various professionals from different departments in clinical settings to manage breast cancer patients properly. Tracing the nodular involvement of breast cancer patients requires radiation source Tc99m labeled with colloidal albumin to be injected at the tumor site. The patient becomes a radiation source for a sufficient time, which concerns the Nuclear Medicine (NM) and surgical staff. The study aims to provide the radiation doses of staff in the NM department during the SLN scintigraphy procedure and obtain an empirical model for calculating the radiation doses to staff in the surgical department from that particular patient. Radiation doses in SLN technique for breast cancer patients are minimal, and a sufficient number of SLN biopsy procedures can be performed by hospital staff within the category of non-radiation workers.

The role of imaging and sentinel lymph node biopsy in patients with T3b-T4b melanoma with clinically negative disease.

Background: Previous studies demonstrate minimal utility of pre-operative imaging for low-risk melanoma; however, imaging may be more critical for patients with high-risk disease. Our study evaluates the impact of peri-operative cross-sectional imaging in patients with T3b-T4b melanoma. Methods: Patients with T3b-T4b melanoma who underwent wide local excision were identified from a single institution (1/1/2005 - 12/31/2020). Cross-sectional imaging was defined as body CT, PET and/or MRI in the perioperative period, with the following findings: in-transit or nodal disease, metastatic disease, incidental cancer, or other. Propensity scores were created for the odds of undergoing pre-operative imaging. Recurrence free survival was analyzed using the Kaplan-Meier method and log-rank test. Results: A total of 209 patients were identified with a median age of 65 (IQR 54-76), of which the majority were male (65.1%), with nodular melanoma (39.7%) and T4b disease (47.9%). Overall, 55.0% underwent pre-operative imaging. There were no differences in imaging findings between the pre- and post-operative cohorts. After propensity-score matching, there was no difference in recurrence free survival. Sentinel node biopsy was performed in 77.5% patients, with 47.5% resulting in a positive result. Conclusion: Pre-operative cross-sectional imaging does not impact the management of patients with high-risk melanoma. Careful consideration of imaging use is critical in the management of these patients and highlights the importance of sentinel node biopsy for stratification and decision making.

Predictors of invasive disease in patients preoperatively diagnosed with ductal carcinoma without stromal invasion, with breast magnetic resonance imaging (MRI) and ultrasound (US).

BACKGROUND: A preoperative diagnosis of ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive disease postoperatively. Our objective was to clarify the predictive factors of invasive disease using preoperative imaging and to investigate the positive ratio of sentinel lymph nodes (SLN) and the incidence of invasive disease. METHODS: The subjects were 402 patients with preoperatively diagnosed ductal carcinoma without stromal invasion who underwent breast surgery with concomitant SLN surgery in January 2007 to December 2016. Of the 306 included patients, all 306 patients underwent preoperative MRI and US assessment. Outcomes were analyzed for significance using univariate and multivariate analyses. RESULTS: Of the 306 patients, 115 (37.6%) had invasive disease and 191 (62.4%) had DCIS only. Of the 115 patients with invasive disease, 5 (4.4%) and 4 (3.5%) had macro- and micrometastases in SLN. On the other hand, of the 191 patients with DCIS, only 1 (0.5%) had a micrometastasis. Predictors of invasive disease in the univariate analysis included having a palpable mass, were varied by biopsy method, having a US hypoechoic mass, MRI enhancement, or MRI large enhanced lesion; the size of the mass enhancement ≥ 1.1 cm or a spread of non-mass enhancement ≥ 3.1 cm (P = 0.003). Predictors of invasive disease in the multivariate analysis included US hypoechoic mass and MRI large enhanced lesion. CONCLUSION: We need to perform SLN biopsy for preoperatively diagnosed DCIS when patients have predictors of invasive disease, but SLN biopsy will no longer be essential for patients when they have no predictors of invasive disease.

Surgical Management of Lymph Nodes in Melanoma.

This article provides a comprehensive evaluation of surgical management of the lymph node basin in melanoma, with historical, anatomic, and evidence-based recommendations for practice.

Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification outcomes. We evaluated the effect of axillary staging procedures and subsequent axillary nodal status in patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) from 1998 to 2013. MATERIALS AND METHODS: The use of SLN biopsy and the nodal status distribution were analyzed in patients with stage T1-T2 ILC and IDC. Logistic regression analysis was performed to determine the independent effect of histologic type on the probability of the presence of isolated tumor cells (ITCs), micrometastases, and macrometastases. RESULTS: A total of 89,971 women were diagnosed, 10,146 with ILC (11%) and 79,825 with IDC (89%). The patients who had undergone SLN biopsy were more frequently diagnosed with ITCs than were those who had undergone axillary lymph node dissection only (odds ratio, 8.8; 95% confidence interval, 7.0-11.2). In 2013, the proportion of patients with ITCs in the axillary nodes was 8% in those with ILC and 4.4% in those with IDC. Patients with ILC were significantly more likely to have ITCs in their axillary lymph nodes than were patients with IDC (odds ratio, 1.8; 95% confidence interval, 1.6-2.0). CONCLUSION: With the introduction of SLN biopsy and the renewed 2002 TNM classification, patients with ILC have been more frequently diagnosed with ITCs than have patients with IDC. The clinical consequence of this finding must be established from further research.

Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases: commentary on the IBCSG 23-01 Trial.

Breast surgical oncologists have rapidly and successfully transitioned from the routine use of axillary lymph node dissection (ALND) to sentinel lymph node (SLN) biopsy for staging the axilla in clinically node negative patients. This approach limits the use of ALND to those patients with pathologically-proven axillary lymph node metastases and has prompted great current interest in whether or not all SLN-positive patients benefit from a completion ALND. Analysis of population-based data shows a decades-long trend towards omitting ALND in patients with low volume axillary disease. Thus, even prior to publication of the results of the ACOSOG Z0011 study and the IBCSG 23-01 study, completion ALND was being performed less frequently for selected patients with nodal micrometastases. Herein we review the contribution of the recently published IBCSG 23-01 study which provides additional data to confirm that for selected patients, mainly those with small, estrogen receptor-positive tumors with low nodal disease burden undergoing breast conservation with radiation and adjuvant systemic therapy, ALND might be avoided safely. This trial, which included small numbers of patients treated by mastectomy without radiation, and lumpectomy with partial breast irradiation, suggests interest in further clinical trials investigating these important patient populations. The study's short median follow-up however, cautions us to be clear in discussion, especially with younger patients who have otherwise biologically favorable tumors, that the long-term outcomes of SLN biopsy alone for low volume axillary disease remains unknown.