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Original Investigation |

Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status A Systematic Review and Meta-analysis

Simone Ribero, MD, PhD1,2; Maria Rosaria Gualano, MD3; Simona Osella-Abate, ScD1,4; Giacomo Scaioli, MD3; Fabrizio Bert, MD3; Martina Sanlorenzo, MD1; Elena Balagna, MD2; Maria Teresa Fierro, MD1; Giuseppe Macripò, MD2; Anna Sapino, MD4; Roberta Siliquini, MD3; Pietro Quaglino, MD1
[+] Author Affiliations
1Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy
2Section of Dermatologic Surgery, Department of Oncology and Hematology, Città della Salute e della Scienza di Torino Hospital, Turin, Italy
3Department of Public Health, University of Turin, Turin, Italy
4Section of Surgical Pathology, Department of Medical Sciences, University of Turin, Turin, Italy
JAMA Dermatol. 2015;151(12):1301-1307. doi:10.1001/jamadermatol.2015.2235.
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Importance  The prognostic significance of regression in primary melanoma has been debated for many years. There is no consensus regarding the need for sentinel lymph node (SLN) biopsy when regression is present within the primary tumor.

Objective  To review the evidence that regression may affect SLN status.

Data Sources  A systematic review was performed by searching in MEDLINE, Scopus, and the Cochrane Library from January 1, 1990, through June 2014.

Study Selection  All studies that reported an odds ratio (OR) or data on expected and observed cases of SLN positivity and histologic regression were included.

Data Extraction and Synthesis  Primary random-effects meta-analyses were used to summarize ORs of SLN positivity and histologic regression. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. The methodologic quality of the studies was assessed according to the Strengthening of Reporting of Observational studies in Epidemiology (STROBE) checklist, and 2 different meta-analyses were performed based on those criteria.

Main Outcomes and Measures  Summary ORs of histologic regression of primary melanoma and SLN status.

Results  Of the 1509 citations found in the search, 94 articles were reviewed, and 14 studies comprising 10 098 patients were included in the analysis. In the combined 14 studies, patients with regression had a lower likelihood to have SLN positivity (OR, 0.56; 95% CI, 0.41-0.77) than patients without regression. On the basis of study quality, we found that patients with regression enrolled in high-quality studies had a lower likelihood to have SLN positivity (OR, 0.48; 95% CI, 0.32-0.72) compared with results of low-quality studies (OR, 0.73; 95% CI, 0.53-1.00). Examination of the funnel plot did not provide evidence of publication bias.

Conclusions and Relevance  The results of this analysis showed that the risk of SLN positivity was significantly lower in patients with histologic regression compared with those without. Regression may be used in these cases to make a selection of which patients should be the most appropriate for this procedure.

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Figure 1.
Flowchart of Article Search and Inclusion
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Figure 2.
Likelihood in Patients With Melanoma of Positive Sentinel Lymph Node (SLN) Biopsy Findings

Illustrated are the standardized odds ratios (ORs) for the studies included in the meta-analysis. Patients with histologic regression of primary melanoma had a lower likelihood of SLN positivity (OR, 0.56; 95% CI, 0.41-0.77; darker dashed vertical line) than patients without regression.

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Figure 3.
Likelihood of Positive Sentinel Lymph Node (SLN) Biopsy Findings in Patients With Melanoma by Study Quality

Illustrated are the standardized odds ratios (ORs) for the high- and low-quality studies included in the meta-analysis. Patients with regression enrolled in high-quality studies had a lower likelihood of SLN positivity (OR, 0.48; 95% CI, 0.32-0.72; darker dashed vertical line) than similar patients enrolled in low-quality studies (OR, 0.73; 95% CI, 0.0.53-1.00; darker dashed vertical line).

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Figure 4.
Funnel Plot of the Studies Included in the Meta-analysis

The funnel plot displays points (each representing an included study) that are evenly and symmetrically distributed, thus showing the absence of study bias and suggesting that the results of the studies are reliable. Ln indicates natural log; OR, odds ratio; SE, standard error.

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