Treatment of metastatic liver tumors using stereotactic ablative radiotherapy

Table 1 Prospective clinical trials in the literature studying stereotactic ablative radiotherapy in liver metastases and their results

Ref.	Design	No of patients	Tumor size	SABR dose	Toxicity	Outcomes
Scorsetti et al[15]	Phase II (preliminary report)	61 (76 tumors)	1.8-134.3 cm3 (mean 18.6 cm3)	75 Gy in 3 fractions	No case of RILD. Twenty-six percent had grade 2 transaminase increase (normalised in 3 mo). Grade 2 fatigue in 65% patients, one grade 3 chest wall pain which regressed within 1 year.	1-yr LC94, 22-mo LC 90.6%
Goodman et al[16]	Phase I (HCC and liver mets)	26 (19 liver mets)	0.8-146.6 mL (median, 32.6 mL)	Dose escalation, 18-30 Gy (1 fr)	No dose-limiting toxicity 4 cases of Grade 2 late toxicity (2 GI, 2 soft tissue/rib)	1-yr local failure, 3% 2-yr OS, 49% (mets only)
Ambrosino et al[17]	Prospective cohort	27	20-165 mL (median, 69 mL)	25-60 Gy (3 fr)	No serious toxicity	Crude LC rate 74%
Lee et al[18]	Phase I-II	68	1.2-3090 mL (median, 75.9 mL)	Individualized dose, 27.7-60 Gy (6 fr)	No RILD, 10% Grade 3/4 acute toxicity No Grade 3/4 late toxicity	1-yr LC, 71% Median survival, 17.6 mo
Rusthoven et al[19]	Phase I-II	47	0.75-97.98 mL (median, 14.93 mL)	Dose escalation, 36-60 Gy (3 fr)	No RILD, Late Grade ¾ < 2%	1-yr LC, 95% 2-yr LC, 92% Median survival, 20.5 mo
Høyer et al[10]	Phase II (CRC oligomets)	64 (44 liver mets)	1-8.8 cm (median, 3.5 cm)	45 Gy (3 fr)	One liver failure, two severe late GI Toxicities	2-yr LC, 79% (by tumor) and 64% (by patient)
Méndez Romero et al[20]	Phase I-II (HCC and mets)	25 (17 liver mets)	1.1-322 mL (median, 22.2 mL)	30-37.5 Gy (3 fr)	Two Grade 3 liver toxicities	2-yr LC, 86% 2-yr OS, 62%
Herfarth et al[21]	Phase I-II	35	1-132 mL (median, 10 mL)	Dose escalation, 14-26 Gy (1 fr)	No significant toxicity reported	1-yr LC, 71% 18-mo LC, 67% 1-yr OS, 72%

SABR: Stereotactic ablative radiotherapy; RILD: Radiation induced liver disease; CRC: Colorectal cancer; HCC: Hepatocellular carcinoma; GI:Gastrointestinal; LC: Local control.

Table 2 Organ at risk constraints in various prospective trials depending on their fractionation schemes[10,15,19,21,28-29,31]

Normal Liver(Liver- CTV-RFA cavities)	D30% = 6-12 Gy, D50% = 4-7 Gy	V15 Gy < 700 mL	30% < 21 Gy, 50% < 15 Gy	V15 Gy < 700 mL	V15 Gy < 700 mL	V5 Gy ≤ 700 mL, Dmean < 15 Gy	V15 Gy < 700 mL	V21 Gy < 700 mL
Stomach	Dmax ≤ 12 Gy	NA	D5 mL < 21 Gy	Dmax ≤ 30 Gy	D1 mL < 21 Gy	Dmax < 30 Gy; D5 mL < 22.5 Gy	V21 Gy < 1%	Dmax ≤ 32 Gy , D10 mL < 28 Gy
Bowel	Small bowel Dmax ≤ 35 Gy	D < 5% volume < 20 Gy	D5 mL < 21 Gy	Dmax ≤ 30 Gy	D1 mL < 21 Gy	Dmax < 30 Gy	Duodenum, small bowel V21 Gy < 1%	Duodenum: Dmax ≤ 32 Gy; D5 mL< 18 Gy Jejunum/ileum: Dmax ≤ 35 Gy, D5 mL ≤ 19.5 Gy Colon: ≤ 38 Gy, D20 mL ≤ 25 Gy
Esophagus	Dmax ≤ 14 Gy	NA	D5 mL < 21 Gy	NA	D1 mL < 21 Gy	NA	V21 Gy < 1%	Dmax ≤ 35 Gy, D5 mL < 27.5 Gy
Kidney	NA	75% volume of each kidney < 5 Gy	NA	Total kidney D35% < 15 Gy	Total kidney D35% < 15 Gy	NA	V15 Gy < 35% for both kidneys	Renal hilum/vascular trunk < 2/3 ≤ 23 Gy Renal cortex (right and left): 200 mL < 17.5 Gy (3.5 Gy/fraction)
Spinal cord	NA	Dmax < 12 Gy	NA	Dmax ≤ 18 Gy	Dmax < 18 Gy	Dmax ≤ 20 Gy	D0.1 cm3 < 18 Gy	Dmax ≤ 30 Gy, D0.25 mL < 22.5 Gy
Heart/ pericardium	NA	NA	D5 mL < 21 Gy	NA	D1 mL < 30 Gy	NA	V30 Gy < 1%	Dmax ≤ 38 Gy, D15 mL < 32 Gy
Skin	NA	NA	NA	NA	NA	NA	NA	Dmax ≤ 32 Gy, D10 mL < 30 Gy
Great vessels	NA	NA	NA	NA	NA	NA	NA	Dmax ≤ 53 Gy, D10 mL < 47 Gy
Chest wall	NA	NA	NA	NA	NA	NA	D30 cm3 < 30 Gy	NA

CTV: Clinical target volume; Dx%: Dose to x%; Dx mL/cm³: Dose to x mL/cm³; RFA: Radiofrequency ablation; NA: Not available.