Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.

BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS: We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72-0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80-0.93). CONCLUSIONS: We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I).

PURPOSE: As clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. METHODS: SLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). RESULTS: The median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. CONCLUSION: Central review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Impact of Time Between Diagnosis and SLNB on Outcomes in Cutaneous Melanoma.

BACKGROUND: Hypothetically, delay between melanoma diagnosis and SLNB could affect outcomes, either adversely by allowing growth and dissemination of metastases, or beneficially by allowing development of an anti-melanoma immune response. Available data are conflicting about the effect of SLNB delay on patient survival. Our objective was to determine whether delay between initial diagnosis and SLNB affects outcomes in patients with cutaneous melanoma. STUDY DESIGN: We performed query and analysis of a large prospectively maintained database of patients with primary cutaneous melanomas undergoing SLNB. An independent dataset from MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was used for validation. Primary outcomes included disease-free survival and melanoma-specific survival. RESULTS: Early and delayed SLNB were defined as less than 30 and 30 or more days from initial diagnosis, respectively. There were 2,483 patients that met inclusion criteria. Positive sentinel lymph nodes were identified in 17.4% (n = 432). Among all patients, 42% had SLNB 30 or more days after diagnosis and 37% of positive sentinel lymph nodes were at 30 or more days. No differences in sex, anatomic site, or histopathologic features were identified between the 2 groups. There was no difference in melanoma-specific survival or disease-free survival between those undergoing early or delayed SLNB. Examination of MSLT-1 trial data similarly demonstrated no difference in survival outcomes. CONCLUSIONS: This, the largest study on this subject to date, found no adverse impact on long-term clinical outcomes of patients due to delay of SLNB beyond 30 days. The MSLT-1 data confirm this result. Patients can be reassured that if the operation is performed 30 or more days after diagnosis, it will not cause harm.

Lung cancer biomarkers: FISHing in the sputum for risk assessment and early detection.

This perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) discusses the role of sputum-based biomarkers in the risk assessment and early detection of lung cancer. The importance of the detection of sputum epithelial chromosomal aneusomy by fluorescence in situ hybridization (FISH) as a potential risk or early-detection biomarker is discussed in the context of other biomarkers and models in lung carcinogenesis. The presently reported findings on FISH in sputum cells are an important contribution worthy of further investigation in defined clinical settings.