The predictive role of comprehensive genomic profiling in angiosarcoma immunotherapy
Authors
- 1 BostonGene, Corp., Waltham, USA
- 2 The University of Texas MD Anderson Cancer Center, Houston, USA
Abstract
Angiosarcomas are rare and aggressive tumors with high risk of recurrence and metastasis that lack effective long-term therapy standards. Growing evidence suggests that immune checkpoint inhibitors (ICI) hold promise as therapeutic options for angiosarcomas [1][2]. Moreover, the tumor microenvironment (TME) landscape in angiosarcomas may contribute to the prediction of tumor response to ICI [3]. Here, we investigated genomic and TME features of angiosarcomas using comprehensive genomic profiling to reveal their potential predictive values for treatment strategies.
Methods:
Retrospective analysis of BostonGene Tumor Portrait™ test reports, which included data from whole exome and whole transcriptome sequencing and comprehensive profiling [3], was performed for 39 samples from angiosarcoma patients. Genomic alterations were identified, and tumors were classified into TME subtypes to define immune and stromal characteristics. For 4 patients with available data on response to prior immunotherapy regimens, associations between TME profiles and the response to ICI and its duration were assessed.
Results:
Samples of primary angiosarcoma (31/39) and radiation-induced angiosarcoma (8/39) patients with cutaneous (13/39) and non-cutaneous (26/39) subtypes were studied. Importantly, genetic alterations critical for targeted therapy selection were uncovered (Table 1). Transcriptomic-based TME classification revealed 67% of angiosarcoma samples (26/39) with immune-enriched (IE) microenvironments, as characterized by high levels of immune infiltration (including cytotoxic effector cells), low to high prevalence of stromal and fibrotic elements, and medium levels of cancer-associated fibroblasts. These features may be associated with potential benefits from ICI therapy. The remaining 33% of samples (13/39) demonstrated a fibrotic (F) TME subtype with minimal immune infiltration and high prevalence of stromal elements. Only 35% of samples (14/39) had high PD-L1 mRNA expression (relative expression at ≥90th percentile according to internal sarcoma cohort). Moreover, 4 samples exhibited high tumor mutational burden (TMB). Response data to prior immunotherapy showed that patients with partial response (PR, N=1) and stable disease (SD, N=1) had an IE TME subtype. Progressive disease (PD) was observed in 2 angiosarcoma patients (IE subtype N=1, F subtype N=1, Table 2).
Conclusions:
The BostoneGene Tumor Portrait™ test revealed possible associations between TME subtypes and immunotherapy response in angiosarcomas. Particularly, immune-enriched tumors may be conducive to more targeted and efficient treatment selection, pending future validation. Angiosarcoma tumor profiling also uncovered potentially targetable and clinically relevant alterations in these tumors, which may expand treatment options.
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