Biochemical Safety of SBRT to Multiple Intrahepatic Lesions for Hepatocellular Carcinoma

Figures & data

Table 1 3-Fraction Liver SBRT Dose Constraints

Organ	Dose Constraint
Bowel	30 Gy < 1 cc
Esophagus	30 Gy < 1 cc
Kidney	14 Gy < 50% volume
	Dmax < 30 Gy
Spinal Cord	Dmax < 15 Gy
Stomach	30 Gy < 1 cc
Conformality Index	< 1.60
Liver	At least 700 cc of liver minus PTV receiving no more than 15 Gy

Abbreviations: SBRT, stereotactic body radiation therapy; Dmax, the maximum point dose; PTV, planning target volume.

Table 2 Dosimetric Characteristics for the Entire Cohort

Prescription Dose / No. of Fractions	No. of Lesions
45 Gy / 3	49
50 Gy / 10	1
40 Gy / 5	1
35 Gy / 5	2
27.5 Gy / 5	2
25 Gy / 5	1
Median PTV (per target)	29.4 mL (range: 5.2–258 mL)
Median Mean Liver Dose (per plan)	6.9 Gy (range: 1.5–14.9 Gy)
Median Cumulative Mean Liver Dose	11.4 Gy (range: 5.2–20.4 Gy)
Median V15Gy (per plan)	170 mL (range: 24–511 mL)
Median Cumulative V15Gy	318 mL (range: 96–683 mL)
Median Veff (per plan)	0.080 (range: 0.019–0.213)
Median Cumulative Veff	0.155 (range: 0.053–0.350)

Abbreviations: PTV, planning target volume; V15Gy, the volume of liver receiving 15Gy or higher; Veff, the effective volume.

Table 3 Baseline Characteristics Comparison for Those That Received SBRT in a Single Course versus Multiple Courses

Characteristic	Single SBRT Course (%), N = 11	Multiple SBRT Courses (%), N = 14	p value
Sex
Male	6 (55)	9 (64)	0.93
Female	5 (45)	5 (36)
Tumor size
Median (range)	2.0 cm (1.1–5.2 cm)	1.9 cm (1–3.9 cm)	0.94
Cirrhosis Etiology
Hepatitis C	5 (45)	8 (57)	0.13
Hepatitis B	1 (9)	0
ETOH	2 (18)	1 (7)
NAFLD	0	2 (14)
Multiple	3 (27)	9
Etiologies	0	2 (14)
Other	0	1 (7)
Hepatic Local-Regional Therapy Prior to SBRT
TACE/TARE	2 (18)	5 (36)	0.37
Resection	2 (18)	3 (21)
RFA	4 (36)	6 (43)
CP Prior to First SBRT
A5	6 (55)	9 (64)	0.42
A6	2 (18)	1 (7)
B7	3 (27)	2 (14)
B8	0	2 (14)
BCLC
A	4 (36)	4 (29)	1.0
C	7 (63)	10 (71)

Abbreviations: SBRT, stereotactic body radiation therapy; ETOH, alcohol included; NAFLD, non-alcoholic fatty liver disease; TACE, transarterial chemoembolization; TARE, transarterial radioembolization; RFA, radiofrequency ablation; CP, Child–Pugh; BCLC, Barcelona Clinic Liver Cancer.

Table 4 Dosimetric Characteristics and Pre-SBRT ALBI Compared for Patients That Received Single and Multiple Courses of SBRT

	Single SBRT Course	Multiple SBRT Courses	p value
Median Prescription Dose	45 Gy (range: 28–45 Gy)	45 Gy (range: 25–50 Gy)	0.60
Median Pre-SBRT ALBI Score	−2.5 (range: −3.1 - −1.5)	−2.8 (range: −3.4 - −1.3)	0.94
Pre-SBRT ALBI Grade
1	7	6	1.0
2	7	5
3	0	0
Median Cumulative V15Gy	167 mL (range: 49–405 mL)	414 mL (range: 127–683 mL)	0.20
Median Cumulative Veff	0.086 (range: 0.041–0.180)	0.18 (range: 0.095–0.320)	0.22
Median Cumulative PTV	39 mL (range: 9–120 mL)	107 mL (range: 31–308 mL)	0.24
Median Cumulative MLD	7.8 Gy (range: 3.2–15 Gy)	13 Gy (range: 8–20 Gy)	0.21

Abbreviations: V15Gy, volume of liver receiving 15 Gy; Veff, effective volume; PTV, planning target volume; MLD, mean liver dose.

Table 5 Dosimetric Characteristics for the 4 Patients Experiencing an Increase in CP of ≥2 Points

Patient 1
Radiation Prescription	27.5 Gy / 5 fractions
Liver Volume	2298 mL
pFLV	2186 mL
Total PTV*	80 mL
Cumulative V15Gy	317 mL
Cumulative mean liver dose	9.14 Gy
Cumulative Veff	0.174
CP / ALBI grade pre-SBRT	B7 / 2
CP / ALBI grade 3 months	B9 / 3
CP / ALBI grade 6 months	Deceased
Patient 2
Radiation Prescription	45 Gy / 3 fractions
Liver Volume	1097 mL
pFLV	1731 mL
Total PTV*	35 mL
Cumulative V15Gy	175 mL
Cumulative mean liver dose	10.3 Gy
Cumulative Veff	0.082
CP / ALBI grade pre-SBRT	B7 / 2
CP / ALBI grade 3 months	N/A
CP / ALBI grade 6 months	C10 / 2
Patient 3
Radiation Prescription	45 Gy / 3 fractions
Liver Volume	2066 mL
pFLV	1900 mL
Total PTV*	61 mL
Cumulative V15Gy	260 mL
Cumulative mean liver dose	12.6 Gy
Cumulative Veff	0.169
CP / ALBI grade pre-SBRT	A6 / 2
CP / ALBI grade 3 months	B8 / 2
CP / ALBI grade 6 months	B7 / 3
Patient 4
Radiation Prescription	45 Gy / 3 fractions
Liver Volume	1170 mL
pFLV	1720 mL
Total PTV*	285 mL
Cumulative V15Gy	443 mL
Cumulative mean liver dose	13.8 Gy
Cumulative Veff	0.189
CP / ALBI grade pre-SBRT	B7 / 2
CP / ALBI grade 3 months	C11 / 3
CP / ALBI grade 6 months	B7 / 2

Notes: *Refers to the sum of all target PTVs for the respective patient.