Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma - 17/02/20

Doi : 10.1016/j.jaad.2019.12.072

Anthony T. Nguyen, MD, PhD ^a,^b, Michael Luu, MPH ^b,^c, Diana J. Lu, MD ^a,^b, Omid Hamid, MD ^d,^e, Jon Mallen-St. Clair, MD, PhD ^b,^f, Mark B. Faries, MD ^d, Nima M. Gharavi, MD, PhD ^g, Allen S. Ho, MD ^b,^f, Zachary S. Zumsteg, MD ^a,^b,^⁎
^a Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California
^b Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
^c Department of Biostatistics and Bioinformatics, Cedars-Sinai Medical Center, Los Angeles, California
^e The Angeles Clinic and Research Institute, Los Angeles, California
^d Department of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, California
^f Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, California
^g Department of Dermatology, Cedars-Sinai Medical Center, Los Angeles, California

^∗Correspondence to: Zachary S. Zumsteg, MD, Department of Radiation Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048.Department of Radiation OncologyCedars-Sinai Medical Center8700 Beverly BlvdLos AngelesCA90048

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Abstract

Background

Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for the number of metastatic LNs, which is a primary driver of survival in multiple cancers.

Objective

To determine the impact of the number of metastatic LNs on survival in MCC.

Methods

Patients with MCC undergoing surgery were identified from the National Cancer Database (NCDB). The association between metastatic LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived by using recursive partitioning analysis. MCC patients undergoing surgery in the Surveillance, Epidemiology, and End Results (SEER) Program were used as validation cohort.

Results

Among 3670 patients in the NCDB, increasing metastatic LN number was associated with decreased survival (P < .001). Mortality risk increased continuously with each additional positive LN when using multivariable, nonlinear modeling. According to a novel staging system derived via recursive partitioning analysis, the hazard ratio for death in multivariable regression compared with patients without LN involvement was 1.24 (P = .049), 2.08 (P < .001), 3.24 (P < .001), and 6.13 (P < .001) for the proposed N1a (1-3 metastatic LNs with microscopic detection), N1b (1-3 metastatic LNs with macroscopic detection), N2 (4-8 metastatic LNs), and N3 (≥9 metastatic LNs), respectively. This system was validated in the SEER cohort and showed improved concordance compared with the American Joint Committee on Cancer, Eighth Edition.

Limitations

Retrospective design.

Conclusions

Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.

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Key words : immunotherapy, lymph node staging, Merkel cell carcinoma, National Cancer Database, radiation, SEER

Abbreviations used : AJCC 8E, CI, ENE, HR, LN, MCC, NCDB, OS, RPA, SD, SEER

Plan

Materials and methods

Number of positive metastatic LNs

Metastatic LN features

Proposed nodal staging system

Discussion

Limitations

Conclusions

	Funding sources: None.
	Disclosure: Dr Faries is on the advisory board for Novartis, Regeneron, Pulse Bioscience, and Delcath Systems. Dr Zumsteg was on the external advisory board for the Scripps Proton Therapy Center and has consulted for EMD Serono. Dr Nguyen; Mr Luu; and Drs Lu, Hamid, Mallen-St. Clari, Gharavi, and Ho have no conflicts of interest to declare.
	IRB approval status: Reviewed and deemed exempt by the Cedars-Sinai IRB.
	Reprints not available from the authors.