1921MO - Patterns of care, outcome and molecular landscape of PATZ1-rearranged sarcomas identifies two prognostic profiles: A cohort study from the French Sarcoma Group (FSG)

Background

PATZ1 rearranged sarcomas (PRS) belong to the “round cell sarcomas with EWSR1–non-ETS fusions” group in 2020's WHO classifications. With only small case series (<10 cases) reporting deep clinical and histological heterogeneity, uncertain prognosis and absence of standard of care, PRS imperatively require further clinico-molecular characterization.

Methods

Pediatric and adult patients from 13 French centers with a diagnosis of PRS from 2011 to March 2023 were included. All PRS diagnosis were histologically and molecularly reviewed by 4 expert pathologists. Patients and tumors characteristics were collected from the national NETSARC+ database (netsarc.sarcomabcb.org) and whole exome-RNAseq was performed with FFPE material.

Results

Seventeen patients were included with a mean follow up of 44 months including 16 with EWSR1::PATZ1 and one with MN1::PATZ1 fusions. Clinical data were heterogeneous in term of baseline clinical characteristics, histopathology, management and outcome. In univariate analyses, age, tumor size, FNCLCC-grade, adjuvant systemic therapy for non-metastatic disease did not correlate to overall survival (OS) whereas stage, Ki67 and some transcriptomic signatures -relative to cell cycle- did. A group of patients with metastasis or Ki67>30% had aggressive clinical course and poor responses to treatment (whether Ewing-like regimen or other). A distinct group of patients had indolent profiles and were long-term free of recurrence (>5years) after surgery alone without adjuvant chemo/radiotherapy.

Table: 1921MO

Univariate analysis of OS using the Cox model: Median OS is 33.5 months (range 5 :120)

1 level of significance: p>0.05:ns; p<0.05:*, p<0.01:**;p< 0.001:**

Conclusions

Our study suggests that the natural history pf PRS differs from Ewing sarcomas. We reveal that some good prognosis PRS are cured with surgery alone while others are aggressive. Stage and ki67 should help to identify those patients while further molecular analyzes are pending.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Dufresne: Non-Financial Interests, Project Lead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, Project Lead, Translational research program: Bayer. J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmun, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. M. Brahmi: Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on GIST treatment in 2019: Bayer; Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on immunotherapy: Amgen. All other authors have declared no conflicts of interest.