Low Risk For Nodal Metastasis Research Articles

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

BackgroundSentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease.Patients and MethodsA total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics.ResultsA total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III–IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC.ConclusionsIn our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.

The Role of Surgical Axillary Staging Prior to Immediate Breast Reconstruction in the Era of De-Escalation of Axillary Management in Early Breast Cancer.

Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction (IBR) is associated with postoperative complications. Although the incidence of node-positive breast cancer is declining, a separate sentinel lymph node biopsy (SLNB) is still performed before mastectomy when IBR is planned, in order to evaluate nodal status and the need for PMRT. This study assessed the impact of staged SLNB on the breast reconstructive planning, and presents common clinicopathological characteristics of breast cancer with macrometastatic nodal spread where staged SLNB would be beneficial to indicate PMRT. Medical records of breast cancer patients scheduled for mastectomy and IBR at Skåne University Hospital, Sweden, from November 2014 to February 2020, were reviewed. Of 92 patients, node-positive disease was present in 15 (16%). Fifty-three patients underwent staged SLNB before mastectomy and IBR, and 10 (19%) presented with nodal metastasis. All patients with macrometastatic sentinel nodes were presented with palpable, multifocal, ER+ breast carcinoma of no special type with tumor size > 17.0 mm. Overall, four women received PMRT after verified metastasis by staged SLNB, and IBR was cancelled for three patients. These findings question the benefit of routine staged SLNB before mastectomy and IBR in breast cancer populations within established mammography screening programs with low risk of nodal metastasis.

The solid variant of papillary thyroid carcinoma: a multi-institutional retrospective study.

The definition of papillary thyroid carcinoma, solid variant (PTC-SV) varies from >50% to 100% of solid/trabecular/insular growth (STI). We aimed to identify prognostic factors and to establish an appropriate STI cutoff for PTC-SV in this multi-institutional study of 156 PTCs with STI. Nodal metastases were seen in 18% and were associated with a higher percentage of papillary and STI. When substratified by infiltration/encapsulation status, the STI percentage did not impact the risk of nodal metastasis. pN1 stage was seen in 51% of infiltrative tumours and 1% of encapsulated lesions. Overall, PTC with STI had an excellent prognosis. The 10-year disease-free survival (DFS) was 87% in the entire cohort, 94% in encapsulated lesions, and 76% in infiltrative tumours. The STI percentage did not impact DFS. Fifty-four patients had noninvasive encapsulated lesions with 2-100% STI. None developed recurrence. Encapsulated lesions were enriched with RAS mutations (54%), whereas infiltrative lesions lacked RAS mutations (4%). The BRAF V600E mutation was an infrequent event, being seen in 11% of the entire cohort. In PTC with STI, the determining factor for nodal metastasis and DFS is the encapsulation/infiltration status rather than the STI percentage. Encapsulated noninvasive tumours with STI follow an indolent course with a very low risk of nodal metastasis and recurrence. Overall, PTC with STI has an excellent prognosis, with a 10-year disease-specific survival (DSS) and DFS of 96% and 87%, respectively. Therefore, the classification of SV-PTC as an aggressive PTC subtype may be reconsidered.

5: LOCAL ENDOSCOPIC RESECTION IS INFERIOR TO GASTRECTOMY FOR EARLY CLINICAL STAGE T1A AND T1B GASTRIC ADENOCARCINOMA: A PROPENSITY-MATCHED STUDY

Abstract Background and aim The role of ER in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus gastrectomy in node negative cT1a and cT1b gastric adenocarcinoma. Methods Data from the National Cancer Database (2010–2015), was used to identify patients with clinical T1aN0 (n = 2,927; ER, n = 1,157; gastrectomy, n = 1,770) and T1bN0 (n = 2,915; ER, n = 474; gastrectomy, n = 2,441) gastric adenocarcinoma. Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias. Results ER for cT1a and cT1b cancers was performed more frequently over time. Rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared to ER for cT1a cancers (HR: 0.79, 95% CI: 0.66–0.95, P = 0.013), and corresponding 5-year survival for gastrectomy and ER were 72% and 66% (P = 0.013), respectively. For cT1b cancers, gastrectomy had a significantly longer survival compared to ER (HR: 0.77, 95% CI: 0.63–0.93, P = 0.008) and the corresponding 5-year survival for gastrectomy and ER were 60% and 50% (P = 0.013), respectively. Conclusion This study demonstrates ER inferior long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis and thus would maximally benefit from ER.

Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma.

The specificity of sentinel lymph node biopsy (SLNB) for detecting lymph node metastasis in head and neck melanoma (HNM) is low under current National Comprehensive Cancer Network (NCCN) treatment guidelines. Multiple machine learning (ML) algorithms were developed to identify HNM patients at very low risk of occult nodal metastasis using National Cancer Database (NCDB) data from 8466 clinically node negative HNM patients who underwent SLNB. SLNB performance under NCCN guidelines and ML algorithm recommendations was compared on independent test data from the NCDB (n=2117) and an academic medical center (n=96). The top-performing ML algorithm (AUC=0.734) recommendations obtained significantly higher specificity compared to the NCCN guidelines in both internal (25.8% vs. 11.3%, p < 0.001) and external test populations (30.1% vs. 7.1%, p < 0.001), while achieving sensitivity >97%. Machine learning can identify clinically node negative HNM patients at very low risk of nodal metastasis, who may not benefit from SLNB.

Validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary

BackgroundIn patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) serves as an important technique to asses disease stage and to guide adjuvant systemic therapy. A model using clinicopathologic and gene expression variables (CP-GEP; Merlin Assay) has recently been introduced to identify patients that may safely forgo SLNB. Herein we present data from an independent validation cohort of the CP-GEP model in Swedish patients. MethodsArchival histological material (primary melanoma tissue) from a prospectively collected cohort of 421 consecutive patients with pT1-T4 melanoma undergoing SLNB between 2006 and 2014 was analyzed using the CP-GEP model. CP-GEP combines Breslow thickness and patient age with the expression levels of eight genes from the primary melanoma. Stratification is based on their risk for nodal metastasis: CP-GEP Low Risk or CP-GEP High Risk. ResultsThe SLNB positivity rate was 13%. Of 421 primary melanomas, the CP-GEP model identified 86 patients as having a low risk for nodal metastasis. In patients with pT1-2 melanomas, the SLNB reduction rate was 35.4% (95% CI: 29.4–41.8) with a negative predictive value (NPV) of 96.5% (95% CI: 90.0–99.3). Among patients with pT1-3 melanomas, CP-GEP suggested a SLNB reduction rate of 24.0% (95% CI: 19.7–28.8) and a NPV of 96.5% (95% CI: 90.1–99.3). Only one of 118 pT3 tumors was classified as CP-GEP Low Risk, and all pT4 tumors were classified as being high risk for nodal metastasis. ConclusionThis study demonstrates that CP-GEP can identify patients with a low risk for nodal metastasis. Patients with pT1-2 melanomas have the highest clinical benefit from using the test, where 35% of the patients could forgo a SLNB procedure.

Lymph node involvement in gastric adenocarcinoma.

Endoscopic management of early gastric cancer is limited by the risk of lymph node metastasis. We aimed to examine the incidence and predictors of nodal metastasis in early gastric adenocarcinoma in a large national US cohort. Cases were abstracted from the National Cancer Database from 2004 to 2016. The incidence and predictors of lymph node involvement for patients with Tis, T1a, and T1b tumors were examined. A total of 202,216 cases of gastric adenocarcinoma were identified in the NCDB. Cases with unknown patient or tumor characteristics, presence of other cancers, and prior neoadjuvant chemotherapy or radiotherapy were excluded. 1839 cases of Tis, T1a, and T1b tumors were identified. Lymph node metastases were present in 18.1% of patients. Lymphovascular invasion (LVI), high-grade histology, stage T1b, and larger size (> 3cm) were independently associated with an increased risk of nodal metastasis on multivariate analysis (P < 0.05). The presence of LVI was the strongest predictor of nodal metastasis with an OR (95% CI) of 5.7 (4.3-7.6), P < 0.001. No lymph node metastasis was found in any Tis tumors. Small T1a low-grade tumors with no LVI had a low risk of nodal metastasis (0.6% < 2cm and 0.9% < 3cm). In this large national cohort, size, lymphovascular invasion, higher grade histology, and T stage were independently associated with lymph node metastasis. For patients with low-grade tumors, < 3cm, without lymphovascular invasion, the risk of nodal involvement was very low, suggesting that this Western cohort could be considered for endoscopic resection.

Treatment and survival outcomes of ceruminous carcinomas of the external auditory canal: a SEER database analysis and literature review.

Ceruminous carcinomas of the external auditory canal (EAC), encompassing adenoid cystic carcinoma (ACC), ceruminous adenocarcinoma (CA), and mucoepidermoid carcinoma (MEC), are extremely rare with little known regarding the influence of demographics, tumor characteristics, and treatment on survival. This study aimed to summarize existent data and describe prognostic factors affecting survival in ceruminous carcinoma. Cases of ceruminous carcinoma of the EAC in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed to provide demographic, cancer-related, and treatment data and assess their influence on disease-specific and overall survival. A literature review was alsoperformed. No significant difference in overall survival (OS) existed for localized versus regional disease, tumor type, or use of radiation therapy. In those with ACC, distant disease had a lower OS compared to regional disease. On review of the literature, local recurrence was a common finding with a low risk for nodal metastasis in ACC and CA. In conclusion,local recurrence wascommondespite aggressive surgical intervention (± radiation therapy); overall survival was unaffected by radiation therapy, tumor type, or local versus regional disease; and more cases of MEC are needed for analysis.

Validation of the Skåne University Hospital nomogram for the preoperative prediction of a disease-free axilla in patients with breast cancer.

BackgroundAxillary staging via sentinel lymph node biopsy (SLNB) is performed for clinically node-negative (N0) breast cancer patients. The Skåne University Hospital (SUS) nomogram was developed to assess the possibility of omitting SLNB for patients with a low risk of nodal metastasis. Area under the receiver operating characteristic curve (AUC) was 0.74. The aim was to validate the SUS nomogram using only routinely collected data from the Swedish National Quality Registry for Breast Cancer at two breast cancer centres during different time periods.MethodThis retrospective study included patients with primary breast cancer who were treated at centres in Lund and Malmö during 2008–2013. Clinicopathological predictors in the SUS nomogram were age, mode of detection, tumour size, multifocality, lymphovascular invasion and surrogate molecular subtype. Multiple imputation was used for missing data. Validation performance was assessed using AUC and calibration.ResultsThe study included 2939 patients (1318 patients treated in Lund and 1621 treated in Malmö). Node-positive disease was detected in 1008 patients. The overall validation AUC was 0.74 (Lund cohort AUC: 0.75, Malmö cohort AUC: 0.73), and the calibration was satisfactory. Accepting a false-negative rate of 5 per cent for predicting N0, a possible SLNB reduction rate of 15 per cent was obtained in the overall cohort.ConclusionThe SUS nomogram provided acceptable power for predicting a disease-free axilla in the validation cohort. This tool may assist surgeons in identifying and counselling patients with a low risk of nodal metastasis on the omission of SLNB staging.

Validation of CP‐GEP (Merlin Assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: A U.S. cohort study

BackgroundApproximately 85% of melanoma patients who undergo a sentinel lymph node biopsy (SLNB) are node‐negative. Melanoma incidence is highest in patients ≥65 years, but their SLNB positivity rate is lower than in younger patients. CP‐GEP, a model combining clinicopathologic and gene expression variables, identifies primary cutaneous melanoma (CM) patients who may safely forgo SLNB due to their low risk for nodal metastasis. Here, we validate CP‐GEP in a U.S. melanoma patient cohort.MethodsA cohort of 208 adult patients with primary CM from the Mayo Clinic and West Virginia University was used. Patients were stratified according to their risk for nodal metastasis: CP‐GEP High Risk and CP‐GEP Low Risk. The main performance measures were SLNB reduction rate (RR) and negative predictive value (NPV).ResultsSLNB positivity rate for the entire cohort was 21%. Most patients had a T1b (34%) or T2a (31%) melanoma. In the T1‐T2 group (153 patients), CP‐GEP achieved an SLNB RR of 41.8% (95% CI: 33.9‐50.1) at an NPV of 93.8% (95% CI: 84.8‐98.3). Subgroup analysis showed similar performance in T1‐T2 patients ≥65 years of age (51 patients; SLNB positivity rate, 9.8%): SLNB RR of 43.1% (95% CI: 29.3‐57.8) at an NPV of 95.5% (95% CI: 77.2‐99.9).ConclusionWe confirmed the potential of CP‐GEP to reduce negative SLNB in all relevant age groups. Our findings are especially relevant to patients ≥65 years, where surgery is often elective. CP‐GEP may guide SLNB decision‐making in clinical practice.

Local Endoscopic Resection is Inferior to Gastrectomy for Early Clinical Stage T1a and T1b Gastric Adenocarcinoma: A Propensity-Matched Study

The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of ER versus gastrectomy in node-negative cT1a and cT1b gastric adenocarcinoma. Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2927; ER: n = 1157, gastrectomy: n = 1770) and T1bN0 (n = 2915; ER: n = 474, gastrectomy: n = 2441) gastric adenocarcinoma. Propensity score matching and Cox multivariable analyses were used to account for treatment selection bias. ER for cT1a and cT1b cancers was performed more frequently over time. The rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared with ER for cT1a cancers (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95; p = 0.013), and corresponding 5-year survival for gastrectomy and ER was 72% and 66%, respectively (p = 0.013). For cT1b cancers, gastrectomy had a significantly longer survival compared with ER (HR 0.77, 95% CI 0.63-0.93; p = 0.008), and the corresponding 5-year survival for gastrectomy and ER was 60% and 50%, respectively (p = 0.013). This study demonstrates ER is inferior in terms of long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis, and would thus maximally benefit from ER.

The modern management of Barrett's oesophagus and related neoplasia: role of pathology.

Modern management of Barrett's oesophagus and related neoplasia essentially focuses upon surveillance to detect early low-risk neoplastic lesions and offering organ-preserving advanced endoscopic therapies, while traditional surgical treatments of oesophagectomy and lymph node clearance with or without chemoradiation are preserved only for high-risk and advanced carcinomas. With this evolution towards figless invasive therapy, the choice of therapy hinges upon the pathological assessment for risk stratifying patients into those with low risk for nodal metastasis who can continue with less invasive endoscopic therapies and others with high risk for nodal metastasis for which surgery or other forms of treatment are indicated. Detection and confirmation of neoplasia in the first instance depends upon endoscopic and pathological assessment. Endoscopic examination and biopsy sampling should be performed according to the recommended protocols, and endoscopic biopsy interpretation should be performed applying standard criteria using appropriate ancillary studies by histopathologists experienced in the pathology of Barrett's disease. Endoscopic resections (ERs) are both diagnostic and curative and should be performed by clinicians who are skilled with advanced endoscopic techniques. Proper preparation and handling of ERs are essential to assess histological parameters that dictate the curative nature of the procedure. Those parameters are adequacy of resection and risk of lymph node metastasis. The risk of lymph node metastasis is determined by depth invasion and presence of poor differentiation and lymphovascular invasion. Those adenocarcinomas with invasion up to muscularis mucosae (pT1a) and those with superficial submucosal invasion (pT1b) up to 500µ with no poor differentiation and lymphovascular invasion and negative margins may be considered cured by endoscopic resections.

Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma.

SummaryBackgroundThe Clinicopathological and Gene Expression Profile (CP‐GEP) model was developed to accurately identify patients with T1–T3 primary cutaneous melanoma at low risk for nodal metastasis.ObjectivesTo validate the CP‐GEP model in an independent Dutch cohort of patients with melanoma.MethodsPatients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP‐GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP‐GEP model were calculated, resulting in CP‐GEP high risk or low risk for nodal metastasis.ResultsIn total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP‐GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9–96.2], with an NPV of 100% (95% CI 72·2–100) in T1, 89·3% (95% CI 72·8–96·3) in T2 and 75·0% (95% CI 30·1–95·4) in T3 melanomas. The CP‐GEP indicated high risk in all T4 melanomas.ConclusionsThe CP‐GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP‐GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.

Significance of Nodal Metastasis in Parotid Gland Acinar Cell Carcinoma.

To evaluate the rate of lymph node metastasis in parotid gland acinar cell carcinoma, to identified factors associated with increased risk of metastasis, and to evaluate the effect of nodal metastasis on survival. This is a retrospective cohort study utilizing data from a large population-based cancer database. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 database. The study cohort included patients with parotid gland acinar cell carcinoma diagnosed between 2000 and 2015. The overall rate of lymph node metastasis was 6.8%. T3/T4 (OR 6.17, 95% CI, 3.03 to 13.16) disease along with High Grade (OR 15.95) disease were associated with increased risk of nodal metastasis. Non-white, non-Black race was associated with decreased risk. Age and sex were not associated with nodal metastasis. Nodal metastasis was associated with worse OS (HR 6.27, 95% CI, 3.85 to 10.20) and DSS (HR 6.96, 95% CI, 3.81 to 12.73) after adjusting for covariates. Parotid gland acinar cell carcinoma carries a low risk of nodal metastasis. Both advanced T stage and high grade are associated with increased risk of nodal metastasis. Nodal metastasis is associated with decreased overall survival. 3 Laryngoscope, 131:E1125-E1129, 2021.

Association of higher axillary pathologic complete response rate with breast pathologic complete response after neoadjuvant chemotherapy.

BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2−, HR+HER2+, HR−HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.

Deselecting Melanoma Patients for Sentinel Lymph Node Biopsy During COVID-19: Clinical Utility of Tumor Molecular Profiling.

The surgical management of newly diagnosed melanoma patients during the coronavirus disease 2019 (COVID-19) pandemic is challenging because access to health care facilities is restricted. Specifically, elective staging procedures such as the sentinel lymph node (SLN) biopsy are difficult to accommodate. As surgical capacity diminishes, surgical guidance for clinicians aims to restrict SLN biopsy in a stepwise fashion.1Melanoma Focus. Coronavirus/COVID-19 Information for Healthcare Professionals. Website.https://melanomafocus.com/members/coronavirus-info-professionalsDate accessed: May 9, 2020Google Scholar,2Society of Surgical Oncology (SSO)Resource for Management Options of Melanoma During COVID-19.https://www.surgonc.org/wp-content/uploads/2020/03/Melanoma-Resource-during-COVID-19-3.30.20.pdfDate accessed: May 9, 2020Google Scholar SLN biopsy is a more complex and time-consuming procedure than is often appreciated because it requires the extensive use of hospital infrastructure and medical specialists. This is shown by a representative case of a Mayo Clinic patient who enrolled in a feasibility study of a molecular method aimed to identify melanoma patients who are so low risk for metastasis that they can safely forgo SLN biopsy (Figure).3Bellomo D. Arias-Mejias S.M. Ramana C. et al.A model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma.JCO Precis Oncol. 2020; 4: 319-334Crossref PubMed Scopus (51) Google Scholar This study was reviewed and approved by the Mayo Clinic Institutional Review Board. Following diagnosis, the patient met with a surgeon, underwent preoperative evaluation with customized testing to ensure a safe recovery, and completed a technetium-99m scintigraphy (single-photon emission computerized tomography [SPECT]) in nuclear medicine combined with computed tomography (CT) to produce SPECT-CT scans. This was followed by SLN biopsy and a wide local excision of the primary tumor in the operating room under general anesthesia. Tissue was paraffin-embedded, sectioned, and stained by hematoxylin and eosin; and melanocyte lineage-specific immunohistochemistry was determined and interpreted by anatomic pathologists. In this case, 3 weeks passed from melanoma diagnosis to finalized SLN biopsy result. Surgery was followed by postoperative care. Aggressive melanoma easily metastasizes, including to SLN, and a positive SLN biopsy result identifies patients with an increased risk of relapse and in need of adjuvant therapy. However, most melanoma does not metastasize to SLN. Nodal metastasis is found in less than 20% of patients who undergo SLN biopsy.3Bellomo D. Arias-Mejias S.M. Ramana C. et al.A model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma.JCO Precis Oncol. 2020; 4: 319-334Crossref PubMed Scopus (51) Google Scholar Although the removal of negative SLN has no discernible therapeutic effect, all patients who undergo SLN biopsy encounter a greater than 10% risk of complications.4Moody J.A. Ali R.F. Carbone A.C. Singh S. Hardwicke J.T. Complications of sentinel lymph node biopsy for melanoma — a systematic review of the literature.Eur J Surg Oncol. 2017; 43: 270-277Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar There is a need for methods to identify patients who are so low risk that they can safely forgo SLN biopsy. We have previously reported on a melanoma risk-stratification approach which combines clincopathologic (CP) variables with a gene expression profile (GEP) from primary diagnostic biopsy tissue.3Bellomo D. Arias-Mejias S.M. Ramana C. et al.A model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma.JCO Precis Oncol. 2020; 4: 319-334Crossref PubMed Scopus (51) Google Scholar Using the CP-GEP test, up to 80% of patients with T1b, 48% of patients with T2a, and 24% of patients with T2b melanoma may forgo the SLN biopsy procedure as they are categorized as low risk for nodal metastasis with an error rate of less than 5%.3Bellomo D. Arias-Mejias S.M. Ramana C. et al.A model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma.JCO Precis Oncol. 2020; 4: 319-334Crossref PubMed Scopus (51) Google Scholar,5Mulder E.E.A.P. Dwarkasing J.T. Hollestein L.M. et al.Validation of a Clinicopathological and Gene Expression Profile (CP-GEP) Model for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.Ann Oncol. 2019; 30 (533-363)Google Scholar Test results are available within days (Figure) and do not require the patient to interact with health care providers. Hospital resources can be prioritized to other tasks. New melanoma risk-stratification methods offer the opportunity to deselect low-risk patients for SLN biopsy. If, on the other hand, molecular testing indicates higher risk, patients can be prioritized for surgery after COVID-19 restrictions are relaxed. Molecular testing is now available through accredited clinical labs in the United States and have the potential to support the management of melanoma patients during the COVID-19 pandemic.

Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

PURPOSEMore than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.PATIENTS AND METHODSGenes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables.RESULTSExpression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%).CONCLUSIONA combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

Management of axilla in breast cancer: the past, present and the future

The role of surgery in treatment of breast cancer has evolved substantially during the last century where radical surgery has gradually been replaced by more conservative approaches. Similarly, surgical treatment of the axilla has changed rapidly especially over last three decades. This is mostly as a result of improvements in understanding of disease behaviour and advances in systemic therapy. Axillary surgery has the dual uses of removing the disease from the axilla and providing information for prognostication which help guide adjuvant therapy. However, surgery to the axilla is associated with substantial morbidly including lymphedema and shoulder stiffness. Hence, less radical approaches for the treatment of the axilla have been of interest. The traditional gold standard of axillary lymph node dissection was challenged by many clinical trials. As result sentinel lymph node biopsy was introduced as an alternative for patients with clinically negative axillae which later became the standard of care for such patients. Subsequent studies proved the safety of omitting completion axillary dissection or replacing with radiotherapy for selected patients with minimal sentinel lymph node involvement. The application of sentinel lymph node biopsy for axillary staging after neoadjuvant chemotherapy has become an area of clinical interest. However, sentinel lymph node biopsy in node-positive patients who become node negative after neoadjuvant chemotherapy is controversial at present due to the relatively high false-negative rate. This however, is improved by careful patient selection combined with some minor changes to the surgical technique of sentinel lymph node biopsy. Novel techniques for lymphatic mapping have shown promising results which further simplify the procedure while improving the accuracy. Axillary reverse mapping, a technique to preserve lymph nodes draining the arm during axillary surgery for breast cancer has been described recently which has further reduced surgical morbidity. The omission of axillary surgery in selected patients with an acceptably low risk of nodal metastasis has gained increasing research interest in the recent past. Furthermore, advances in treatment and newer prognostication techniques have reduced the dependence on axillary nodal status on adjuvant therapy decision-making. This has led to several ongoing clinical trials which will assess the feasibility of avoiding sentinel lymph node biopsy altogether in selected groups of patients without compromising outcomes.

Value and best way for detection of Sentinel lymph node in early stage endometrial cancer: Selective lymphadenectomy algorithm

IntroductionThe cornerstone of treatment for endometrial carcinoma is total abdominal hysterectomy and bilateral salpingo-oophoprectomy. Pelvic lymphadenectomy, with or without para-aortic lymphadenectomy, plays an important role in the surgical staging of endometrial carcinoma, and provides more accurate prognostic information. AimsWe aimed to evaluate the value and techniques for SLN mapping in early stage endometrial cancer with low risk for lymph node metastasis and whether selective or systematic lymphadenectomy is needed according to the results of proposed algorithm. MethodBetween June 2016 and June 2017, 120 patients with early stage endometrial cancer with low risk for nodal metastasis underwent surgical staging. Patients were classified equally according to SLN mapping technique used for injecting the methylene blue dye. Group A included hysteroscopic guided methylene blue injection, Group B included transcervical injection, Group C included subserosal uterine injection and Group D included combined transcervical and subserosal injection. Blue lymph nodes and enlarged suspicious whether stained or non stained ones were dissected for frozen section evaluation done then bilateral pelvic node dissection was done and tissues were sent for pathological examination. ResultsClinical and pathological SLN detection were more with hysteroscopic technique than others and pathological detection was lower than clinical detection in all techniques. Metastatic disease was more common in nodes with suspicious appearance. About 10% of negative suspicious and mapped nodes were associated with positive other nodes for metastasis. ConclusionSLN in endometrial cancer has a role in staging of endometrial cancer with best technique for detection, hysteroscopic guided blue dye injection. SLN can be used in patients with low risk for lymph node metastasis for selective lymphadenectomy. Blue dye labelling using methylene blue dye is good in low resource countries as it is cheap. We recommended the following algorithm for surgical staging in early endometrial cancer with better results than using SLN alone. Stage I type 1, grade 1,2 endometrial cancer should undergo surgical staging with initial evaluation of the peritoneum which if affected, it is stage III with no need for lymphadenectomy. Then, dissection of the blue and suspicious nodes which if any is positive on frozen section, selective same side pelvic and paraaortic nodal dissection should be done. If they are negative, no need for lymphadenectomy. This approach can help patients to avoid the side effects associated with a complete lymphadenectomy. The higher rate of detection using this algorithm is related to combining the suspicions nodes with the stained ones.

Melanocytic tumour with unknown malignant potential--a Danish study of 67 patients.

The aim of our single clinical centre study was to evaluate the risk of local metastases, lymph node metastases and distant metastases in patients diagnosed with melanocytic tumour with unknown malignant potential (MELTUMP). Furthermore, we evaluated several histologic tumour characteristics as potential predictive factors. From 1 January 1999 to 30 June 2011, a total of 67 consecutive patients were diagnosed with MELTUMP in our hospital. In this study, all the pathology slides were reviewed by the same independent expert dermatopathologist. All data were retrieved from patient charts. Four patients (6%) had regional nodal dissemination at the time of the diagnosis. Furthermore, one patient (1%) developed regional spread during follow-up and another patient (1%) died from distant metastases 1 year after diagnosis. We found no predictive factors with regard to histologic tumour characteristics. Our study confirms the low malignant potential of MELTUMP. We found a low risk of nodal metastasis and mortality from distant metastasis during follow-up. We recommend that all patients diagnosed with MELTUMP should be treated according to the guidelines for invasive melanoma.