ESTRO 2024 - Abstract Book

S1839

Clinical - Mixed sites, palliation

ESTRO 2024

1 LHSC, Radiation Oncology, London, Canada. 2 Ottawa Hospital, Radiation Oncology, Ottawa, Canada. 3 Western University, Medical Biophysics, London, Canada. 4 Niagara Health, Radiation Oncology, Niagara, Canada

Purpose/Objective:

Current randomized trials are investigating the use of SABR in patients for up to 10 extracranial oligo-metastatic lesions.[1] However, the safety of SABR for patients with widely metastatic disease (>10 lesions) is unknown. In this novel phase 1 study, we aimed to determine the feasibility and safety of delivering SABR to all polymetastases (>10) in patients whose systemic therapy options had been exhausted or declined.

Material/Methods:

In this phase I trial (NCT04530513) we enrolled patients who were ECOG 0-2, estimated life expectancy >3 months, >10 metastases, and had no standard of care systemic therapy options available. We used a 3+3 design including five dose levels from 6 Gy (6 Gy weekly x 1) to 30 Gy (6 Gy weekly x 5), increasing incrementally by 6 Gy with dose de-escalation mandated if organ-at-risk (OAR) constraints could not be achieved. Dose limiting toxicity (DLT) was defined a priori as any one of the following occurring within the first six weeks post-treatment: a grade 5 event related to treatment, any grade 4 respiratory, hematologic, or hepatobiliary event or more than three instances of grade 3- 4 events in a single patient (CTCAE version 5.0). If ≥ 2/3 patients had a DLT then the MTD would be declared. If 1/3 patients had a DLT then three additional patients would be recruited, the MTD was then declared ≥ 2/6 of patients experienced DLT, or if a dosimetrically acceptable plan was achieved in fewer than half of patients at a given dose level. Secondary endpoints included quality of life (QoL; FACT-G and EQ-5D-5L) at 6-weeks post treatment, progression-free survival (PFS), and overall survival (OS). Overall, 13 patients were enrolled at the following dose levels: 6 Gy (n=0), 12 Gy (n=3), 18 Gy (n=3), 24 Gy (n=4), and 30 Gy (n=3). Seven were male and 6 female, with a median age of 72 (range: 54-82). Planning and treatment delivery was completed in 12/13 patients. In the one patient who did not complete treatment, OAR volume changes were detected before the last fraction, and replanning was recommended but the patient declined, resulting in treatment termination after 3/4 fractions. Across all patients, a total of 206 lesions were treated (median 16 lesions per patient, range: 11-27) involving a median of 2 organ systems (range: 1-5). The median lesion size treated was 1.68 cm3 (range: 0.07-106). Patients required a median of 4 isocenters (range: 2-9). At the 6-week follow-up, 9 patients (69%) had acute treatment toxicity: grade 1 (n=6, 46%) or grade 2 (n=2, 15%; n=1 pneumonitis and n=1 fatigue) and grade 3 neutropenia (n=1, 8%). There were no grade 4 or 5 toxicities. Mean ± SD QoL scores at baseline versus 6-week follow-up were as follows: FACT-G total score of 80.4 ± 21.9 vs. 76.4 ± 21.8 (p=0.009), FACT-G physical score of 22.4 ± 5.7 vs. 20.8 ± 6.2 (p=0.035), FACT-G social score of 22.5 ± 7.7 vs. 22.3 ± 4.9 (p=0.016), FACT-G emotional score of 16.7 ± 4.7 vs. 16.0 ± 5.4 (p=0.453), FACT-G functional score of 18.8 ± 7.2 vs. 17.2 ± 7.9 (p=0.025), a EQ-5D-5L health state score of 77.4 ± 20.9 vs. 68.0 ± 24.2 (p=0.055) and EQ-5D-5L index score of 0.79 ± 0.22 vs. 0.75 ± 0.25 (p=0.09). Overall, there was a statistically significant decrease in QoL in certain domains, but these findings were either not clinically significant, or for the FACT-G total score of borderline significance [2,3]. Results: