Reply to I. Satzger et al
Authors: Rajmohan Murali, Chitra Desilva, John F. Thompson, Richard A. Scolyer
Journal: Journal of Clinical Oncology (2011)

We thank Satzger et al 1 for their interest in our recent report. 2 In their letter, 1 the authors commented on our study and, importantly, tested our proposed Non-Sentinel Node Risk Score (N-SNORE) 2 in their cohort of sentinel node (SN) -positive patients with melanoma.Satzger et al 1 state that they "were surprised by the selection of parameters, because some did not correlate with NSLN [non-sentinel lymph node] positivity in other studies." 1 The parameters were selected based on their association with non-sentinel node (NSN) positivity, initially in univariate analyses and subsequently in a multivariate logistic regression analysis.Point assignment for each of the five parameters contributing to N-SNORE was not arbitrary; rather, it was weighted based on the strength of the association (odds ratio) of each parameter with NSN positivity.We deliberately chose not to select the parameters on the basis of the literature, because as we stated in our paper, although "some clinical, primary tumor, and SN characteristics have been identified as predictors of NSN positivity, there is considerable variation in reported results and in the relative predictive importance of individual factors….The considerable variation in reported predictors of NSN positivity is due to differences in sample size, populations studied, protocols for pathologic processing and examination of primary tumors and SNs, and methods of data analysis, as well as the effects of interobserver variation in pathologic interpretation." 2-5We were also careful not to use different indices of tumor burden in the same model so as to avoid errors resulting from collinearity effects. 6 For these reasons, we selected parameters that were most significantly associated with NSN positivity in the analysis of our cohort.In their summary of our study, Satzger et al 1 describe the five parameters that are components of N-SNORE, including "increasing size of SLN tumor deposit (with cutoffs at 0.05, 2, and 10 mm)." 1 However, the cutoffs in our study were 0.5, 2, and 10 mm.They also comment that "the size of the largest diameter of tumor deposit (Ͼ 10 mm) seemed rather high for micrometastasis, because 90% of metastases in the regional lymph nodes greater than 1 mm can be regularly detected by ultrasound morphology criteria." 1 Our patient cohort comprised all SN-positive patients with melanoma (SN biopsy was performed in all patients with clinically negative SNs).Furthermore, the contention that 90% of SN metastases greater than 1 mm in size can be identified by ultrasound is not supported by our experience 7,8 or that of other groups, including the numerous centers involved in MSLT-II (Multicenter Sentinel Lymphadenectomy Trial II).As we stated in our study, 2 N-SNORE is a proposed score, which will require validation in independent cohorts of SN-positive patients with melanoma before it can be advocated as a tool to direct patient clinical management.Therefore, we welcome the attempt by Satzger et al 1 to validate the N-SNORE system in their patient cohort.However, there are a number of methodologic issues that require clarification.It is unclear what the criteria were for entry of individual parameters into their multivariate logistic regression models.The authors state that they included parameters from our study as well as "maximum size of SLN tumor deposit of 0.1 mm, positivity of SLN by hematoxylin and