(P 387) CLINICAL CHARACTERIZATION OF PATIENTS WITH LEIOMYOSARCOMA HARBORING THE R337H TP53 GERMINATIVE ALTERATION (LI-FRAUMENI SYNDROME) AND THE PROGNOSTIC IMPLICATION USING A PROPENSITY-SCORE MATCHED COHORT

Objective: We seek to characterize the clinical presentation of patients (pts) with leiomyosarcoma (LMS) harboring the R337H TP53 germinative alteration (TP53g) and to analyze the survival outcomes compared to a cohort of pts with wildtype R337H TP53 (TP53wt) LMS.

Methods: We retrospectively reviewed consecutive cases of pts diagnosed with LMS in our hospital from January 2000 to January 2023 who were positive for the R337H TP53 pathogenic variant (PV). In addition, constitutional DNA of pts with LMS stored in the biobank were prospectively evaluated for the mutation. The TP53wt cohort was formed by the cases registered in the institutional database added to the negative cases founded by the biobank samples testing. Overall survival (OS) was defined as the time from treatment initiation until death from any cause. Disease-free survival (DFS) was evaluated for pts with localized disease and defined as the time from first treatment until the date of objective disease progression or death from any cause in the absence of progression. Qualitative variables were compared with chi-square and Fisher exact tests. Propensity score was used to match the patients according to the variables of interest (histology, primary site, age, sex, ECOG, size, extension, grade, neo/adjuvant chemotherapy, neo/adjuvant radiotherapy). Survival was calculated using the Kaplan-Meier method and the curves were compared by the log-rank test.

Results: Ninety-two patients diagnosed with LMS and tested for R337H TP53 status were included of which 30 (32.6%) harbored the R337H TP53 variant. In the TP53g cohort, the median age at diagnosis was 54.5 yo (26–74) and the site of primary lesion was retroperitoneum/pelvis in 23 pts (76.6%). Ninety-three percent of the tumors (n=28) were grade 2 or 3. Most patients (90%) were diagnosed with localized disease. The size of the lesion was 5–10 cm in 9 pts (30%), and 10–15 cm in 12 pts (40%). All the clinical characteristics of included pts and patterns of treatment for localized disease are presented in table 1. At the time of analysis, the median follow-up was 85 months for the whole series (IQR, 51–110 months). Overall, for the 92 pts included in the database, the unadjusted median OS (mOS) was 98 months (95% CI 55.1–140.8), with 122 months (95% CI 60.4–183.5) in TP53g cohort, and 98 months (95% CI not applicable) in TP53wt cohort (p=0.63). After propensity score matching of 60 pts with a 1:1 ratio, demographic, baseline tumor characteristics, and treatment patterns for localized disease were well balanced with no significant differences between the 2 cohorts, except for tumor location, which retained an excess of pts with retroperitoneal tumors in the TP53g cohort, and a higher number of extremities tumors in the TP53wt cohort. In the 1:1 matched population, there was a numerically non-statistically significant difference in mOS between the 2 cohorts: 121 months (95% CI 62.4–179.2) in the TP53g cohort versus 74 months (95% CI 55.5–92.4) in the TP53wt cohort (p=0.31). The median DFS for pts with localized disease at diagnosis was 33 months (95% CI 14.3–51.6) in the TP53g cohort, and 120 months (95% CI not applicable) in the TP53wt cohort (p=0.25).

Conclusion: Our data show that pts with LMS haboring the R337H TP53 germinative PV are more likely to present grade 2/3 tumors located in the retroperitoneum. The presence of the mutation might represent better prognosis for patients in comparison to non-mutated pts, but further study is ongoing to increase the number of pts in the analysis, as well as to compare the prognostic implications of others TP53 PV.