Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma

Figures & data

Table I. Patient and tumour characteristics.

Patient characteristics
Sex
Female	105 (64%)
Male	58 (36%)
Age, median + range	70 years (23–94)
Primary tumour location
Upper arm	6 (4%)
Lower arm	6 (4%)
Hand	2 (1%)
Upper leg	11 (7%)
Knee	5 (3%)
Lower leg	95 (58%)
Foot	33 (20%)
Unknown	2 (1%)
Missing	3 (2%)
Breslow, mean + range	6.0 mm (0.8–137 mm)
Bulky tumour	29 (18%)
N-stage
N2c	95 (58%)
N3	68 (42%)
M-stag
M0	152 (95%)
M1	8 (5%)
Chemo
Melphalan	148 (91%)
Melphalan + TNF-alpha	15 (9%)
Vessel
Axillary	9 (6%)
Brachial	3 (2%)
Femoral	57 (35%)
External iliac	92 (56%)
Subclavian	2 (1%)
Time from primary tumour to  first in-transit, mean (range)	25 months (0–220 months)
Time from first in-transit to ILP,  mean (range)	13 months (0–157 months)

Table II. Response and local toxicity according to perfusion time and temperature.

	120 min		90 min
	41–41.5 °C	39–40 °C	39–40 °C
Response
PR	17 (19%)	7 (29%)	7 (18%)
CR	60 (66%)	15 (63%)	26 (67%)
Wieberdink
II	54 (57%)	17 (71%)	32 (76%)
III	38 (40%)	5 (21%)	10 (24%)
IV	3 (3%)	2 (8%)	0 (0%)

Figure 1. Flow-chart of the 163 included patients divided according to response (CR, complete response; PR, partial response; NC, no change; PD, progressive disease) and subsequent local progression and amputation rate.

Table III. Univariate and multivariate logistic regression of clinical predictive factors for CR after isolated limb perfusion.

	Univariate analysis			Multivariate analysis
Variables	OR	95%CI	p Value	OR	95%CI	p Value
Age (years)	1.00	0.97–1.02	0.83
Gender (female^a vs. male)	1.53	0.74–3.14	0.25
Primary tumour Breslow (mm)	0.91	0.82–1.01	0.07
Primary tumour localisation (distal^a vs. proximal)	0.92	0.32–2.64	0.87
Primary tumour localisation (leg^a vs. arm)	7.01	0.89–55.48	0.07
N-stage (N2c^a vs. N3)	0.48	0.24–0.95	0.04*
Size (non-bulky^a vs. bulky)	0.51	0.22–1.19	0.12
Number of lesions (≤10^a vs. >10)	0.14	0.07–0.32	<0.0001***	0.20	0.07–0.56	0.002**
Wieberdink (Grade II^a vs. grade III)	1.08	0.52–2.23	0.84
Wieberdink (Grade III^a vs. grade IV)	0.73	0.11–4.80	0.74
Time from primary tumour to in-transit metastases (months)	1.00	0.88–1.14	0.97
Time from in-transit to ILP (months)	1.02	0.83–1.26	0.84
Perfusion temperature (41 °C^a vs. 40 °C)	1.20	0.62–2.35	0.59
Perfusion time (120 min^a vs. 90 min)	1.00	0.51–1.96	0.99

^aReference category. *p < 0.05, **p ≤ 0.01, ***p ≤ 0.0001.

Figure 2. Local progression-free survival (LPFS) depending on (A) more or less than 10 in-transit metastases, (B) CR vs no-CR after ILP, (C) proximal or distal localisation of primary tumour. Estimates are calculated by the Kaplan-Meier method and the log-rank test.

Table IV. Univariate and multivariate Cox-regression of clinical prognostic factors for local recurrence after isolated limb perfusion.

	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	p value	HR	95%CI	p value
Age (years)	0.99	0.97–1.00	0.057
Gender (female^a vs. male)	1.20	0.78–1.84	0.40
Primary tumour Breslow (mm)	1.01	1.00–1.02	0.18
Primary tumour localisation (distal^a vs. proximal)	1.92	1.06–3.49	0.03*	1.87	1.03–3.42	0.041*
Primary tumour localisation (leg^a vs. arm)	1.62	0.82–3.23	0.17
N-stage (N2c^a vs. N3)	1.15	0.76–1.74	0.52
Bulky disease (≤4 cm^a vs. >4 cm)	1.51	0.90–2.54	0.12
Number of lesions (≤10^a vs. >10)	2.08	1.34–3.21	0.001**
Type of perfusion (M-ILP^a vs. TM-ILP)	1.75	0.90–3.40	0.10
Wieberdink (Grade II^a vs. grade III)	0.84	0.54–1.30	0.43
Wieberdink (Grade III^a vs. grade IV)	1.06	0.34–3.37	0.92
Complete response (no CR^a vs. CR)	0.20	0.12–0.32	<0.00001***	0.19	0.12–0.32	<0.00001***
Time from primary tumour to first in-transit (years)	0.98	0.90–1.06	0.63
Time from first in-transit to ILP (months)	0.95	0.83–1.08	0.42
Perfusion temperature (41 °C^a vs. 40 °C)	1.17	0.77–1.77	0.46
Perfusion time (120 min^a vs. 90 min)	0.83	0.51–1.37	0.47

^aReference category. *p < 0.05, **p ≤ 0.01, ***p ≤ 0.0001.

Figure 3. Cancer-specific survival depending on (A) sex, (B) lymph-node status, (C) presence of distant metastases, (D) bulky tumour, (E) more or less than 10 in-transit metastases, (F) CR vs. no-CR after ILP. Estimates are calculated by the Kaplan-Meier method and the log-rank test.

Table V. Univariate and multivariate Cox-regression of clinical prognostic factors for cancer-specific survival after isolated limb perfusion.

	Univariate analysis			Multivariate analysis
Variables	HR	95%CI	p Value	HR	95%CI	p Value
Age (years)	1.00	0.98–1.01	0.67
Gender (female^a vs. male)	1.58	1.07–2.33	0.02*
Primary tumour Breslow (mm)	1.00	0.98–1.01	0.62
Primary tumour localisation (distal^a vs. proximal)	1.34	0.71–2.52	0.36
Primary tumour localisation (leg^a vs. arm)	1.33	0.71–2.48	0.37
N-stage (N2c^a vs. N3)	2.35	1.59–3.46	0.00002***	2.08	1.38–3.15	0.001**
M-stage (M0^a vs. M1)	3.67	1.76–7.61	0.0005**
Bulky disease (≤4 cm^a vs. >4 cm)	2.19	1.33–3.60	0.002**	1.84	1.09–3.11	0.02*
Number of lesions (≤10^a vs. >10)	1.81	1.18–2.76	0.006**
Complete response (no CR^a vs. CR)	0.40	0.27–0.61	0.00002***	0.47	0.31–0.72	0.001**
Time from primary tumour to first in-transit (years)	0.93	0.85–1.02	0.13
Time from first in-transit to ILP (months)	0.99	0.84–1.12	0.84
Subsequent reperfusion (no^a vs. yes)	0.72	0.46–1.14	0.16

^aReference category. *p < 0.05, **p ≤ 0.01, ***p ≤ 0.0001.

Table VI. Univariate and multivariate logistic regression of clinical predictive factors for toxicity (Wieberdink grade II vs. III) after isolated limb perfusion.

	Univariate analysis			Multivariate analysis
Variables	OR	95%CI	p Value	OR	95%CI	p Value
Age (years)	1.03	1.00–1.06	0.04*	1.03	1.00–1.06	0.04*
Gender (female^a vs. male)	0.99	0.50–1.99	0.99
CR (no CR^a vs. CR)	1.08	0.52–2.23	0.84
Perfusion temperature (41 °C^a vs. 40 °C)	0.46	0.23–0.93	0.03*
Perfusion time (120 min^a vs. 90 min)	0.48	0.24–0.96	0.04*	0.44	0.22–0.91	0.03*
Type of perfusion (TM-ILP^a vs. M-ILP)	0.81	0.25–2.60	0.72

^aReference category. *p ≤ 0.05.