Harris, Jeremy P.

Hypofractionated radiation therapy regimens should not be used as standard of care for localized soft tissue sarcoma

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

8567 Background: Adjuvant osimertinib (osi) improves disease-free survival (DFS) in patients (pts) with resected, early-stage, EGFR-mutant (EGFRmut) NSCLC, yet the benefit of osi after CRT in pts with unresectable locally advanced NSCLC is unknown. Post-hoc analysis of the PACIFIC trial showed a lack of survival benefit with consolidation durva versus placebo in pts with EGFRmut NSCLC. Comparisons between consolidation durva and EGFR TKIs in unresectable EGFRmut NSCLC following CRT are lacking. Methods: We conducted a multi-institutional retrospective analysis of pts with stage III unresectable EGFRmut NSCLC (exon19 deletion, exon21 L858R), who received EGFR TKI or durva after ≥ 2 cycles of platinum-based chemotherapy plus definitive radiation therapy between 2015-2022. Baseline characteristics including age, sex, smoking history, PD-L1 status, and outcomes on DFS, overall survival (OS), and safety were collected. Multivariable (MVA) cox regression analysis was used for statistical analysis. Treatment-related adverse events (trAE) were defined using CTCAE 5.0. Results: Seventeen pts from 12 institutions received an EGFR TKI (osi, n=15; erlotinib, n=2), and 13 pts received consolidation durva. Median follow-up was 23 months. Median age of all pts was 61 years (IQR:52-72) and 76.7% were female. Most pts in both groups had never-smoked and had adenocarcinoma. All pts received ≥ 60 Gy of radiation with concurrent chemotherapy. PD-L1 expression was ≥ 50% in 1/10 (10%) pts treated with durva vs 6/13 (46.2%) treated with TKI, p=0.09. Median duration on treatment for EGFR TKI and durva was 12.2 months and 4.8 months, respectively. Pts treated with EGFR TKI had significantly longer 24-month DFS versus pts treated with durva after adjusting for stage (3A vs 3B vs 3C) (Table). Any grade tRAE occurred in 58.8% (10/17) of pts treated with EGFR TKI vs 38.5% (5/13) with durva. Grade > 3 tRAE occurred in 15.4% (1 pneumonitis and 1 AST/ALT elevation) of pts treated with durva but in none of pts treated with EGFR TKI. Three pts within each arm came off treatment due to toxicity (EGFR TKI: 1 pneumonitis and 2 dermatitis; durva: 1 of each pneumonitis, Type 1 diabetes, AST/ALT elevation). Conclusions: EGFR TKI therapy after definitive CRT was associated with significantly longer DFS compared to durva in this retrospective study of pts with stage III unresectable EGFRmut NSCLC, without unanticipated safety signals. Follow-up is ongoing and OS outcomes will be evaluated subsequently. Further investigation is warranted to define the optimal therapy for locally advanced EGFRmut NSCLC. [Table: see text]