1173P - NRAS mutation as an independent prognostic factor for resectable Chinese acral melanoma

Background

Acral melanoma (AM) is the most common subtype of Chinese melanoma population, taking up over 50%-60%. Compared to cutaneous melanoma, AM is lack of frequent driven mutation like BRAF alternation which only occurs around 10%. Meanwhile, 10%-15% of AM can harbor NRAS mutation. This single-center retrospective study aims to investigate the survival impact of NRAS mutant status on Chinese AM after receiving radical surgery.

Methods

We retrospectively collected AM patients who received radical surgery in Fudan University Shanghai Center with confirmative genomic information from 2017 to 2021. Information of clinicopathologic factors and recurrence and survival outcomes was retrieved from patients document database of our hospital.

Results

Totally 317 patients were recruited in our study.170 (53.6%) were males and median age was 62 years old (range 26-89). 281 (88.6%) cases had primary lesion at lower extremity. The mean Breslow thickness were 3.9mm and ulceration rate was 65.9%. According to AJCC 8^th staging system, there were 12% Stage I, 32.2% Stage II and 55.8% Stage III. Genomic alternation occured included 71(22.4%) NRAS, 36 (11.4%) BRAF, 33 (10.4%) KIT and the other 177 (55.8%) widetype of these three genes. No statistical difference was observed in most of clinicopathologic factors between NRAS-mut and NRAS-wt patients. However, NRAS-mut group had higher risk of nodal metastasis beyond 1^st tier basin (42.3% vs 27.2, P<0.002).With median follow-up of 22 months, NRAS-mut patients had significantly worse relapse-free survival (RFS, P<0.0001) and overall survival (OS, P=0.010). Distant metastasis-free survival (DMFS) was also numerically reduced but not reached significance (P=0.074). Multivariate analysis showed NRAS mutation was an independent prognostic factors for both RFS (P=0.008) and OS (P=0.025).Among patients receiving adjuvant anti-PD1 monotherapy, median RFS time was significantly worse for NRAS-mut patients (9 months vs 26 months, P<0.0001).

Conclusions

In conclusion, AM harboring NRAS mutation had higher risk of relapse and death as well as reduced efficacy of adjuvant anti-PD1 monotherapy compared to NRAS-wt after radical surgery. NRAS mutation was an independent prognostic factor for resectable Chinese AM population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research was funded by Shanghai Science and Technology Development Funds, grant number 9411951700; LinGang laboratory “Seeking Distinguished Young Scholars” project, grant number LG-QS-202205-11; National Natural Science Foundation of China, grant number 81802636.

Disclosure

All authors have declared no conflicts of interest.