(P 201) PLEOMORPHIC RHABDOMYOSARCOMAS: A NEW ENTITY ASSOCIATED WITH LYNCH SYNDROME? FIRST RESULTS OF SARCLYNCH NATIONAL STUDY

Objective: Historically, sarcomas do not belong to Lynch Syndrome (LS) spectrum. However, we recently published review of literature (Poumeaud et al, Current Opinion in Oncology 2023) reporting unusual high proportion of pleomorphic rhabdomyosarcomas (pRMS) in Lynch patients having developed a sarcoma (10%). The main objective of SarcLynch is to verify these data in real life through GSF-GETO cohort.

Methods: SarcLynch is a French national multicentric retro-prospective cohort describing clinical and tumoral characteristics of sarcomas developed in LS patients. Patients were identified through Netsarc and oncogenetic OfeLy databases. All patients with a proven LS having developed a bone sarcoma (BS) or a soft-tissue sarcoma (STS) were included. Patients with a syndromic variation of LS or Lynch-like syndrome were excluded. All cases were reviewed in a sarcoma expert center.

Results: Eighty-five patients were pre-identified. We present the results obtained on the first 78 patients, included from 15 centers in France. Median age at diagnosis was 51 years old (15-85 y.o). Among patients with available data, 52 (72%) have a personal history of cancer (whom 50 belonging to LS spectrum). Sixty-five patients (83.3%) developed a STS while 13 developed a BS (16.7%). Among STS, undifferentiated pleomorphic sarcomas (UPS, n=18, 27.7%) and pRMS (n=14, 21.5%) are most diagnosed sub-types. Chondrosarcomas (n=6, 46.2%) are most represented BS. Most patients (n=31, 39.8%) present a germinal mutation of MSH2 gene. Mismatch repair somatic phenotype is available for 36 patients in immunohistochemistry (IHC) with 24 patients being deficient mismatch repair (dMMR, 66.7%). Microsatellite instability assessed by Pentaplex-PCR is available for 28 patients, whom 13 are micro-satellite instable (MSI). Eight patients (30.4%) exhibit discrepancy between IHC and PCR assessment. Seven patients (9%) were treated with immune checkpoint inhibitors (ICI, 6 with pembrolizumab and 1 with nivolumab). Six patients responded positively with stable or partial responses. Duration of response varies from 6 to 28 months in patients with significant CPS and tumoral mutational burden (TMB) scores.

Conclusion: These results are consistent with those previously published in literature, with an unusually high proportion of pRMS in LS patients (21.5% vs < 1% in sporadic STS) and in patients with germline mutation of MSH2 (39.8% vs 25% in LS patients). Despite the few patients treated with ICI (n=7, 9%), most of them (n=6, 85.7%) favorably responded to anti-PD1/PD-L1 with some extended responses. Similarly, biomarkers predictive of response to ICI (CPS, TMB) seem to be increased, consistently with LS-carcinomas. First results of SarcLynch report an unusually high proportion of PRM in LS patients, suggesting a possible interest to screen for LS in PRM. A better comprehension of genomic instability in this subgroup is essential and will be performed in SarcLynch-GI study.