2956 - Ablative Radiotherapy in Patients with Large Volume Liver Metastases and in Those with Prior Liver Directed Therapies: An Analysis of Safety and Local Control

J. J. Bassmann^1,2, N. Kim³, S. Chahwan⁴, L. A. Boe⁵, M. Reyngold², M. El Homsi⁴, P. B. Romesser², H. Azhari⁶, A. Wei⁷, W. Jarnagin⁷, C. H. Crane², and C. Hajj²; ¹The Donald and Barbara Zucker School of Medicine, Hempstead, NY, ²Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ³Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Gastroenterology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁷Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Ablative RT (A-RT) has been shown to safely provide favorable local progression-free and overall survival (OS) in pts with liver cancers. Concerns have been raised regarding the safety of A-RT in pts with large liver tumors and in those with prior liver directed therapies. In this work, we assess response and toxicities associated with A-RT to liver metastases (LM). Materials/

Methods: We identified 121 pts treated with A-RT to LM between 2017–2022. We assessed toxicities using CTCAE V5.0. Early radiographic response was measured by a dedicated liver radiologist using RECIST 1.1. Patients with scores of 1, 2, or 3 (complete response (CR), partial response, and stable disease respectively) were grouped as responders.
Results: Median age was 64 yrs (range 25-93), with 63 (52%) males and 58 (48%) females. 63 (48%) pts had large tumors (defined as combined gross tumor volume (GTV) >33cc equivalent to >4cm diameter), and 25 (21%) pts had a GTV/liver volume ratio >10%. Most pts (96%) had prior liver directed therapies. 70 (58%) pts had colorectal primaries. Median fup and OS were 14 and 19 months respectively. Median BED was 120Gy (range 96-225) delivered using SBRT (1-5 fx) or fractionated A-RT (up to 25 fx). Median total GTV volume was 29 cc (range 1-1,863). In correspondence with the RT plan, a median of 1,137 cc (range 478-2,472) of liver minus GTV were spared and mean liver minus GTV dose was exceeded in 17 (13%) pts by a median of 6% (range 0.4-36). For all pts, GTV coverage was excellent (median D95 and V100 of 102% and 99.8% respectively). 90% of pts responded to A-RT at 1st fup (median 60 days) and 98% at 2nd fup (median 128 days). Zero and six pts had a CR at 1^st and 2^nd fups respectively. On univariable analysis, histology, prior liver-directed therapies and dosimetric parameters were not significant predictors of response to A-RT. While GTV volume was significantly associated with response at 1^st fup (p=0.024), this lost significance at 2^nd fup (p=0.13). A-RT to large liver lesions was not associated with more toxicity. No acute grade 4-5 toxicities were noted. Most common acute toxicity was grade 1 fatigue in 72 pts (62%). Long-term toxicities are shown in table 1. Liver function measured using albumin, LFTs, bilirubin and INR levels at 3- and 6-months post RT compared to respective baselines was maintained.
Conclusion: A-RT to LM is safe even in heavily pretreated pts and in patients with large liver tumor volumes. A-RT is associated with an excellent early radiographic response. This response is slightly slow, with more responders noted at 18 weeks vs 8 weeks. Additional local control data will be available at the time of the meeting.

Abstract 2956 – Table 1. Long-Term Toxicities

Toxicities	N = 121 n (%)
Abdominal Pain	30 (25%)
Bile Duct Stricture	2 (1.7%)
Dyspepsia	12 (9.9%)
Chest Wall Pain	5 (4.1%)
Gastric Ulcer	4 (3.3%)
Duodenal Ulcer	3 (2.5%)
Cholangitis	1 (0.8%)
Worst grade of toxicity
1	16 (13%)
2	18 (15%)
3	10 (8.3%)
4	2 (1.7%)
0	75 (62%)