Radiation Oncology

High symptomatic RP with concurrent first-line third‑generation EGFR‑TKI and thoracic RT; dosimetry and drug matter.

In 209 treatment‑naive EGFR‑mutant NSCLC patients receiving first‑line third‑generation EGFR‑TKI with thoracic radiotherapy, grade ≥2 RP occurred in 43.54%. Osimertinib had the highest observed RP rates; aumolertinib and furmonertinib showed lower risks within this cohort. Independent predictors of grade ≥2 RP included ipsilateral lung V5 ≥ 35.93% and GTV ≥ 12.62 mL; V30 ≥ 24.61% and larger GTV predicted grade 3. Median progression‑free survival was 26.7 months and did not differ between the TKIs in this retrospective single‑center series. 1

IDC‑P and tertiary GP5 may identify patients with limited relative benefit from salvage radiotherapy.

Central pathology review of 167 JCOG0401 patients found IDC‑P and tertiary Gleason pattern 5 associated with reduced relative SRT benefit on time to treatment failure. Absence of IDC‑P was associated with substantial SRT benefit (HR 0.330, 95% CI 0.161–0.673), whereas presence showed no significant benefit (HR 0.771). Absence of tertiary GP5 showed a very large SRT benefit (HR 0.099), while tertiary GP5 attenuated that effect. These are exploratory interaction analyses from a secondary pathology review and require prospective validation before changing practice. 2

Atypical EGFR and non‑G12C KRAS mutations are common in a diverse resected lung adenocarcinoma cohort.

Among 292 resected lung adenocarcinomas with NGS, Hispanic ethnicity independently associated with EGFR positivity (aOR 3.88). Of EGFR‑positive tumors, 26% were atypical variants, with numerically higher proportions in Black (37%) and Hispanic (27%) patients. KRAS mutations were predominantly non‑G12C (58%), highlighting many patients lack G12C‑specific targeted options. Findings underscore the need for broad NGS panels and inclusive trial designs to avoid leaving subgroups without actionable therapies. 3