Volume specific response criteria for brain metastases following salvage stereotactic radiosurgery and associated predictors of response

Figures & data

Table I. Baseline patient and tumour characteristics (n =70 patients, 178 metastases).

Characteristics	No.	%
Median age (range)	56 years	(25–79)
Female	39	56
Male	31	44
Performance status
• KPS <70	5	7
• KPS 70–80	17	25
• KPS 90–100	48	69
Primary histology
• Lung primary	33	47
• Breast primary	9	13
• Renal cell or melanoma primary	13	19
• Other or unknown primary	15	21
Systemic disease status
• No evidence of systemic disease	1	1
• Stable systemic disease	24	36
• Progressive systemic disease	22	30
• Synchronous systemic disease	23	33
Targets treated per patient: median (range)	1	(1–18)
Median individual target V3D (range)	0.7 cm^3	(0.01–22.7)
Median cumulative target V3D (range)	3.6 cm^3	(0.1–39.1)
WBRT prior to SRS	161	95
No prior WBRT	17	5
Median survival (range)	15.3 months	(4.6–23.3)

KPS, karnofsky performance status; SRS, stereotactic radiosurgery, supratentorial deep lesions where those located within the basal ganglia, thalamus, or hypothalamus; V_3D, segmented volume; WBRT, whole brain radiotherapy.

Table II. RECIST response criteria according to Therasse et al. [1] and the derived percent volume changes that co-relate with RECIST for Vc and V_3D based on the present analysis.

Response	RECIST^†	Vc	V3D
Complete response (CR)	100% decrease	100% decrease	100% decrease
Partial response (PR)	≥30% decrease	≥65% decrease	≥58.5% decrease
Stable disease (SD)	<30% decrease or	<65% decrease or	<58.5% decrease or
	<20% increase	<75% increase	<71.5% increase
Progressive disease (PD)	≥20% increase	≥75% increase	≥71.5% increase

^†RECIST definitions are based on the described established criteria according to percent change in maximum diameter [1]. The V_3D (segmented volume) and V_c (calculated volume) response definitions are those derived experimentally by our analyses using RECIST as the reference.

Table III. Target response rates according to RECIST, Vc and V_3D at each specified follow-up.

	RECIST (%)				Vc (%)				V3D (%)
Time point (months)	CR	PR	SD	PD	CR	PR	SD	PD	CR	PR	SD	PD
3	8	22	61	8	8	22	60	9	8	17	64	10
6	14	23	50	13	14	23	47	15	14	22	52	12
9	14	24	47	15	14	24	44	18	14	23	47	16
12	14	22	47	18	14	23	43	20	14	23	44	19
18	13	22	47	19	13	22	44	22	13	22	44	20
24	13	22	47	19	13	22	44	22	13	22	44	21

CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; V_c, calculated volume; V_3D, segmented volume. Note the derived criteria in percent volume change that yielded the consistency in the responses observed in this table at each follow-up are summarised in Table II.

Figure 1. Intracranial progressive disease rates according to baseline segmented contrast volume (V_3D) >6 cm³ vs. ≤6 cm³.

Figure 2. Overall survival distribution based on cumulative tumour baseline segmented contrast volume (V_3D) ≥3 cm³ vs. <3 cm³.

Table IV. Predictors of progressive local disease.

	Local control	RECIST	Vc	V3D
Factor	%	Global p-value	Global p-value	Global p-value
Primary cancer
• Breast	75	0.599	0.408	0.91
• RCC or melanoma	91
• Lung	82
• Other or unknown	75
Location
• Supratentorial	83	0.405	0.77	0.477
• Infratentorial	75
Dose (cGy)
• 1200–1500	87	0.15	0.217	0.078
• 1800–2100	78
• 2400	79
Metastasis diameter (cm)
• <3.0	86	0.006	N/A	N/A
• >3.0	57
Metastasis volume (cm^3)
• ≤6	86	N/A	0.088	0.043
• >6	50
Cumulative volume (cm^3)
• <3.0	83	N/A	0.716	0.618
• 3.0–6.0	66
• 6.0–10.0	44
• >10.0	56

N/A, not applicable; RCC, renal cell carcinoma; V_c, calculated volume; V_3D, segmented volume.

Table V. Prognostic factors for overall survival.

Factor	% alive	Global p-value
Primary cancer
• Breast	73	0.423
• RCC or melanoma	71
• Lung	70
• Other or unknown	67
Age
• <60 years	63	0.634
• ≥60 years	64
KPS (baseline)
• <70	60	0.246
• 70–80	71
• 90–100	60
RPA (baseline)
• 1	64	0.422
• 2	64
• 3	50
GPA (baseline)
• ≤2.5	60	0.236
• >2.5	67
Number of targets
• 1–3	65	0.099
• ≥4	54
Previous WBRT
• No	67	0.896
• Yes	62
Maximum diameter (cm)
• <3.0	66	0.126
• ≥3.0	0
Cumulative V3D (cm^3)
• <3.0	83	0.02
• ≥3.0	49

GPA, graded prognostic index; KPS, karnofsky performance score; RCC, renal cell carcinoma; RPA, recursive prognostic analysis index; V_3D, segmented volume; WBRT, whole brain radiotherapy.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.

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