Lymph node management in melanoma has been controversial for over 100 years. Earlier findings of our study group have contributed to current understanding of several cancers and have established current standards for treatment of melanoma with improved prognostic assessment, identification of patients for appropriate interventions, and prevention of treatment-related morbidity. The current proposal will complete the definition of optimal surgical therapy of regional lymph nodes.
These aims will be achieved through the second Multicenter Selective Lymphadenectomy Trial (MSLT2).
Aim 1) To determine if immediate completion lymph node dissection enhances the outcomes of patients with melanoma sentinel node metastases The primary endpoint of MSLT2 is melanoma-specific survival comparing patients with positive sentinel lymph nodes (SLN) who are treated by immediate completion lymph node dissection (CLND) to those who are followed using clinical and ultrasound examination. Secondary endpoints include disease-free survival, time to recurrence in the regional lymph node basin, quality of life, and safety.
Aim 2) To establish and validate optimal methods of SLN evaluation and prognosis determination Although SLN biopsy has improved staging accuracy in melanoma, """"""""gold standard"""""""" methods for SLN evaluation are not established. The rich data available in trial databases have allowed evaluation of several leading candidate parameters for nodal assessment and prognosis. MSLT2 will validate the methods and allow more precise determination of the need for more therapy or follow up.
Aim 3) To determine the utility of novel, currently non-standard evaluation measures: 3a) RT-PCR evaluation of SLN: Some patients with SLN that are negative by standard pathologic evaluation recur and die of melanoma. Retrospective studies suggest that RT-PCR evaluation of lymph nodes can discriminate patients who are or are not at substantial risk of recurrence. Validation of these data prospectively in MSLT2 has the potential to revolutionize SLN evaluation. 3b) Ultrasound follow up of at-risk nodal basins: MSLT2 is systematically evaluating the utility of serial ultrasound of lymph node basins in which a positive sentinel node was identified. The significance of these objectives cannot be overstated. MSLT1 has spared many patients unnecessary surgery, morbidity, anxiety and expense. The current trial will establish a similar standard for patients with sentinel node metastases and either confirm the need for immediate CLND or allow the majority of patients to avoid it.

Public Health Relevance

Current standard treatment for patients who have had melanoma metastasize to initial or sentinel lymph nodes incudes remove of the remaining lymph nodes in the same area, called completion lymph node dissection. The current proposal will determine through a prospective, randomized, Phase III trial whether that surgery is necessary or if close observation of the area is sufficient. It will also establish the optimal method of determining prognosis in these patients and the possible utility of additional testing including reverse- transcriptase polymerase chain reaction (RT-PCR) and lymph node ultrasound.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA189163-01
Application #
8768419
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (M1))
Program Officer
Song, Min-Kyung H
Project Start
2014-09-23
Project End
2019-08-31
Budget Start
2014-09-23
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$1,780,788
Indirect Cost
$646,270
Name
John Wayne Cancer Institute
Department
Type
DUNS #
556074458
City
Santa Monica
State
CA
Country
United States
Zip Code
90404
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Faries, Mark B (2018) Completing the Dissection in Melanoma: Increasing Decision Precision. Ann Surg Oncol 25:585-587
Faries, Mark B; Han, Dale; Reintgen, Michael et al. (2018) Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials. Clin Exp Metastasis 35:431-442
Deutsch, Gary B; Tyrell, Richard; Yost, Samuel et al. (2018) Predicting the incidence and timing of central nervous system disease in metastatic melanoma: Implications for surveillance and preventative therapy. J Am Acad Dermatol 78:419-421
Faries, Mark B; Cochran, Alistair J; Thompson, John F (2017) Regarding complications following completion lymphadenectomy. Eur J Surg Oncol 43:2374-2375
Jones, Maris S; Jones, Peter C; Stern, Stacey L et al. (2017) The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma. Ann Surg Oncol 24:2089-2094
Nelson, Daniel W; Stern, Stacey; Elashoff, David E et al. (2017) Impact of Time Between Diagnosis and SLNB on Outcomes in Cutaneous Melanoma. J Am Coll Surg 225:302-311
Jones, Maris S; Lee, Jihey; Stern, Stacey L et al. (2017) Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes? J Am Coll Surg 225:149-158
Faries, Mark B; Thompson, John F; Cochran, Alistair J et al. (2017) Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med 376:2211-2222
Ozao-Choy, Junko; Nelson, Daniel W; Hiles, Jason et al. (2017) The prognostic importance of scalp location in primary head and neck melanoma. J Surg Oncol 116:337-343

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