Genomic Profiling Useful in Minimizing RIE and Treating Those With ESCC

Comprehensive genomic guided treatment of esophageal squamous cell carcinoma may help decrease radiation-induced esophagitis rates.

Among individuals with esophageal squamous cell carcinoma (ESCC), comprehensive genomic profiling is useful in guiding treatment and minimizing radiation-induced esophagitis (RIE), according to a study published in the International Journal of Radiation Oncology, Biology, Physics.

This retrospective, single-center study included 183 individuals (median age, 60.5 years; 75.41% men; 80% stage III) from China with unresectable ESCC, using pretreatment tumor tissue samples and targeted sequencing of a pancancer gene panel consisting of 474 cancer-related genes. For validation, the study researchers used an independent cohort of 84 individuals (median age, 59 years; 77.38% men) with stage II-III ESCC. Endpoints included overall, progression-free, logoregional relapse-free, and distant metastasis-free survival; genomic features; and RIE toxicity RIE features. All endpoints were analyzed for associations, with non-normally distributed data analyzed using the Wilcoxon rank sum test.

Among the study participants, 87% showed evidence of cell-cycle-pathway gene alterations. Other commonly altered pathways included the PI3K-AKT (n=84, 45.9%), RKT-RAS (n=52, 28.4%), NRF2 (n=67, 36.6%), NOTCH (n=70, 38.3%), and homologous recombination repair (HRR; n=37; 20.2%) pathways. An association was identified between HRR pathway alterations and shortened progression-free survival.

Our collective data offer new insights into the optimization of treatment management and prognostic assessments of patients with ESCC.

The median overall survival for mutation vs wild-type was 21.80 vs 34.73 months, respectively (hazard ratio [HR], 2.12; 95% CI, 1.25-3.60; P =.004). An association was identified between altered RTK-RAS pathways and lower overall survival among those treated with chemoradiotherapy. The median overall survival for mutation vs wild-type was 23.70 vs 33.50 months, respectively (HR, 1.92; 95% CI, 1.20-3.07; P =.006).

ESCC tumors with alterations in HRR pathways also showed enriched apolipoprotein B mRNA editing enzyme, and catalytic polypeptide (APOBEC) signatures 2 and 13. These elevated signatures and altered HRR pathway were associated with poor prognoses among those treated with definitive chemoradiotherapy. An independent sequence cohort validated the correlation of HRR pathway alterations and/or APOBEC signature with poor overall and progression-free survival. Of particular importance was the association between altered HRR pathway and high-grade RIE toxicity.

Limitations to this study include a lack of correction of P values via false discovery rate testing, a retrospective study design, and the use of a single institution.

The study authors wrote, “Our collective data offer new insights into the optimization of treatment management and prognostic assessments of patients with ESCC.”

References:

Li L, Sun J, Liu N, et al. Clinical outcome-related cancer pathways and mutational signatures in patients with unresectable esophageal squamous cell carcinoma treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. Published online September 24, 2022. doi: 10.1016/j.ijrobp.2022.07.1835