1076O - Primary analysis of the EORTC 1208 Minitub trial: Prospective registry of sentinel node (SN) positive melanoma patients with minimal SN tumor burden

Background

Retrospective studies have shown the prognostic value of SN tumor burden (van der Ploeg et al. JCO 2011). There are different ways to assess SN tumor burden, e.g. as the microanatomic location (Dewar et al. JCO 2004) or the diameter of the largest deposit (van Akkooi et al. Ann Oncol 2006). The aim of this study was to determine outcomes of patients (pts) with minimal SN tumor burden, managed without complete lymph node dissection (CLND).

Methods

Melanoma pts with minimal SN tumor burden were prospectively followed. Pts were seen every 4 months (yr 1-2), 6 months (yr 3-5) and annually (yr 6-10). They had baseline imaging. An ultrasound of the lymph nodes at every visit was advised. The hypothesis was that the cumulative incidence of distant metastasis at 5 years was lower than 20% in pT2-3 pts.

Results

Between 2015 and 2021, 296 pts were recruited from 21 centers in 9 countries; 17 CLND and 279 observation (OBS), incl. 201 with pT2-3; 149 were eligible (main group). Central pathology review demonstrated 33 pts (11%) did not harbor metastases (macrophages/benign capsule nevi) and 36 (12%) no minimal SN tumor burden. Median follow-up was 4.5 yrs (IQR 3.0 – 5.5 yrs). The cumulative incidence of distant metastasis and death due to melanoma at 5 yrs were 15% (90% CI 10-21%, one-sided p=0.096) and 8% in the main group and 8% & 6% among all patients from OBS group with AJCC8 stage IIIA. SN tumor burden (> 0.1 vs < 0.1 mm)[HR 2.35, P=0.022] and AJCC stage [HR 3.09 for IIIB vs IIIA and 5.01 for IIIC vs. IIIA, P65 yrs 34 (23) 71 (25) Male 66 (44) 127 (46) AJCC8 stage I-II 0 (0) 19 (7) IIIA 87 (58) 152 (54) IIIB 41 (28) 56 (20) IIIC 16 (11) 45 (16) Missing 5 (3) 7 (3) Breslow pT1 (4.00mm) 0 (0) 26 (9) Ulceration Absent 122 (82) 227 (81) Present 22 (15) 42 (15) Unknown 5 (3) 10 (4) Number of SN+ 0 0 (0) 19 (7) 1 138 (93) 242 (87) >1 11 (7) 18 (6) Systemic therapy 24 (16) 42 (15)

Conclusions

Central review revealed overdiagnosis in 11%. This first and only prospective study of melanoma pts with minimal SN tumor burden demonstrated low rates of distant metastases or death. SN tumor burden was an independent prognostic factor, and it should be considered to be added to future staging systems for improved prognostication, allowing to spare low-risk stage III pts the potential toxicity of adjuvant therapy.

Clinical trial identification

NCT01942603.

Editorial acknowledgement

Legal entity responsible for the study

EORTC.

Funding

EORTC.

Disclosure

A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Personal, Advisory Board: Neracare, SkylineDx; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. D. Massi: Financial Interests, Personal, Advisory Board: Sakura, Sun Pharma; Financial Interests, Personal, Invited Speaker: Sanofi, Novartis. M. Kicinski: Financial Interests, Institutional, Research Grant: MSD, BMS; Financial Interests, Institutional, Funding: Pierre Fabre, Immunocore, JnJ. H. Peach: Financial Interests, Personal, Other, Survey on melanoma pathways and adjuvant immunotherapy 12/04/24: MSD; Financial Interests, Personal, Member of Board of Directors, This is my private practice company. My work is mainly skin oncology, I have no sponsorship or financial agreement with any other company: Peach Skin Clinic; Non-Financial Interests, Member of Board of Directors, UK based melanoma charity - I am on the trust board: Melanoma Focus. B. van de Wiel: Non-Financial Interests, Advisory Role, no activities in last two years: BMS. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. A.M.M. Eggermont: Financial Interests, Personal, Advisory Board: Agenus, BioInvent, Boehringer Ingelheim Ingelheim, BioNTech, Brenus, CatalYm, Galecto, Egle, Eikon Therapeutics, Imcheck, IO Biotech, ISA Pharmaceuticals, Merck&Co, MSD, Pfizer, Pierre Fabre, IQVIA, Pierre Fabre, GenOway, Sairopa, Scancell, SkylineDX, Scorpion, TigaTX, Trained Therapeutics DIscovery; Financial Interests, Personal, Stocks/Shares: IO Biotech, Sairopa, SkylineDX. All other authors have declared no conflicts of interest.