TOPLINE:

A new study found that the degree of immune enrichment predicted radiosensitivity. The radiosensitivity index (RSI), a validated genomic marker, was higher in pretreatment immune-enriched triple-negative breast cancers that did not achieve a pathologic complete response to neoadjuvant therapy, and these tumors showed increased predicted radiotherapy resistance.

METHODOLOGY:

• Radiotherapy reduces locoregional recurrence and improves survival for patients undergoing breast-conserving surgery and those with nodal involvement — and the RSI (based on the expression of 10 genes) reliably predicts radiosensitivity. However, most patients with triple-negative breast cancer undergo neoadjuvant chemoimmunotherapy, and it is unknown whether RSI predicts response to neoadjuvant therapy or whether such therapy alters RSI and predicted radiosensitivity.
• Researchers analyzed total RNA from pretreatment core needle biopsy specimens of 197 patients (median age, 51 years) with triple-negative breast cancer treated with neoadjuvant systemic therapy. Paired posttreatment tumor tissue was available from 58 patients who did not achieve a pathologic complete response.
• RNA exome sequencing was performed, and RSI was computed using a published 10-gene algorithm. Stromal tumor-infiltrating lymphocytes were scored on pretreatment and posttreatment samples by an expert breast pathologist following international consensus guidelines.

TAKEAWAY:

• Cluster analysis of RSI genes identified two groups of pretreatment tumors: immune-depleted and immune-enriched. Patients with immune-enriched tumors had significantly higher pathologic complete response rates (67.2% vs 43.2%; P = .001), and immune-enriched tumors also had greater predicted radiosensitivity — lower tumor cell survival after an acute exposure of 2 Gy (SF2Gy) than immune-depleted tumors (median SF2Gy, 0.42 vs 0.56; P < .0001).
• Across the cohort, RSI changes after neoadjuvant therapy were variable. But among patients with initially immune-enriched tumors that did not achieve a pathologic complete response, predicted radiosensitivity declined between pretreatment and posttreatment samples.
• Modeling predicted the posttreatment radiation dose needed to achieve 5‑year probability of control of 94.7%. Compared with a pretreatment dose of 50 Gy, posttreatment doses of 50, 60, and 66 Gy would achieve equivalent control in 61%, 77%, and 84% of immune-depleted tumors vs 37%, 67%, and 74% of immune-enriched tumors, respectively.

IN PRACTICE:

“While radiotherapy doses after neoadjuvant systemic therapy are often prescribed based on pretreatment clinical distribution of disease, radiographic and/or pathologic evidence of treatment response, and extent of surgery, our results suggest that integration of therapy-induced genomic and immunologic changes may allow a more personalized approach to radiotherapy,” the authors of the study concluded.

SOURCE:

The study, led by Shane R. Stecklein, MD, PhD, University of Kansas Medical Center, Kansas City, Kansas, was published online in International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS:

Paired posttreatment sequencing data were unavailable for 26 patients due to various factors, including unavailability of surgical specimens and disease progression during neoadjuvant therapy, which could affect the analysis comparing pre- and posttreatment changes.

DISCLOSURES:

The study received support from The University of Kansas Cancer Center, the National Institutes of Health, University of Kansas Medical Center Research Institute, The Kansas Institute for Precision Medicine, Team Michelle, and Merck Sharp & Dohme LLC. Some authors reported receiving honoraria or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.