Hyperthermic isolated limb perfusion in locally advanced limb soft tissue sarcoma: A 24-year single-centre experience

Figures & data

Table 1. Patient characteristics.

Characteristics	N	(%)
Sex
Male	55	47
Female	62	53
Age
<50 yrs	42	35,9
≥50 yrs	75	64,1
Tumour location
Upper limb	28	23.9
Lower limb	89	76.1
Tumour burden
Unifocal	82	70.1
Multifocal	35	29,9
Presentation
Primary	92	78.6
Recurrent	25	21.4
Tumour size
<10 cm	60	51.3
≥10 cm	57	48.7
Distant metastases	17	14.5
Previous treatments
Chemotherapy	6	5.1
Radiotherapy	9	7.7
Combination	3	2.6
Stage
T1b	13	11.1
T2b	104	88.8
Grading
I–II	12	10.3
III	105	89.7
Histotype
Leiomyosarcoma	23	19.7
Liposarcoma^a	20	17.1
MPNST	17	14.5
Pleomorphic sarcoma	16	13.7
Synovial sarcoma	14	11.9
Lymphangiosarcoma	7	5.9
Myxofibrosarcoma	4	3.4
EMC	4	3.4
Haemangiopericytoma	3	2.5
Rhabdomyosarcoma	2	1.7
Other histotypes	8	6.4

EMC, extra-skeletal myxoid chondrosarcoma; MPNST, malignant peripheral nerve sheath tumours.

^aDe-differentiated or myxoid liposarcomas.

Table 2. Tumour response and local toxicity according to drug schedule.

			Locoregional toxicity (Wieberdink) (no. of pts, %)
Drug schedule (no. of patients)	HILP duration (min)	ORR (%)	1–2	3	4	5
Doxorubicin (n = 47)	90	72.3	38 (80.9)	8 (17.0)	1 (2.1)	0
TNF-α^a+ doxorubicin (n = 30)	90	78.6	24 (80.0)	4 (13.4)	1 (3.3)	1 (3.3)
TNF-α^b+ L-PAM (n = 40)	60	75.0	37 (92.5)	1 (2.5)	0	0

L-PAM, melphalan; ORR, overall response rate (pathological evaluation of surgical specimen of 115 resected patients); TNF-α, tumour necrosis factor alpha.

^aHigh dose (3 or 4 mg for the upper or lower extremity, respectively).

^bLow dose (1 mg).

Table 3. Local and systemic toxicity according to drug schedule in 117 sarcoma patients after hyperthermic isolated limb perfusion.

	Toxicity by CTAE grade
	Doxorubicin (N = 47)		TNF-α + doxorubicin (N = 30)			TNF-α + L-PAM (N = 40)
	Any	G3–4	Any	G3–4	G5	Any	G3–4
	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Local
Intraoperative artery injury	1 (2.1)	0	1 (3.3)	0	–	0	0
Intraoperative vein injury	2 (4.2)	0	1 (3.3)	0	–	2 (5)	0
Skin rash	7 (14.9)	2 (4.2)	8 (26.7)	4 (13.3)	–	5 (12.5)	1 (2.5)
Pain – limb	20 (42.5)	7 (14.9)	8 (26.7)	6 (20)	–	8 (20)	3 (7.5)
Cellulitis infection	8 (17)	2 (4.2)	12 (40)	4 (13.3)	–	6 (15)	3 (7.5)
Lymphocele	4 (8.5)	0	3 (10)	0	–	2 (5)	0
Peripheral arterial ischaemia	0	0	2 (6.7)	0	–	0	0
Phlebitis	1 (2.1)	0	1 (3.3)	0	–	1 (2.5)	0
Thrombosis	2 (4.2)	0	0	0	–	0	0
Limb oedema	4 (8.5)	1 (2.1)	6 (20)	2 (6.7)	–	4 (10)	0
Neuropathy – sensor	8 (17)	1 (2.1)	6 (20)	1 (3.3)	–	2 (5)	0
Neuropathy – motor	6 (12.8)	0	3 (10)	0	–	0	0
Extremity – upper (function)	7 (14.9)	0	6 (20)	0	–	8 (20)	0
Extremity – lower (gait/walking)	5 (10.6)	0	6 (20)	0	–	5 (12.5)	0
Systemic
Nausea/vomiting	5 (10.6)	0	4 (13.3)	0	–	4 (10)	0
Pneumonitis	0	0	1 (3.3)	0	–	0	0
Thrombocytopaenia	0	0	1 (3.3)	0	–	0	0
Leucopaenia	1 (2.1)	0	2 (6.7)	0	1 (3.3)	1 (2.5)	0
Infection – urinary tract	1 (2.1)	0	0	0	–	1 (2.5)	0
Increased creatinine	2 (4.2)	0	1 (3.3)	0	–	0	0

CTAE: common terminology criteria for adverse event. DOX: doxorubicin. L-PAM: melphalan.

Figure 1. Flow chart of patient outcome. CR, complete response; CT, chemotherapy; HILP, hyperthermic isolated limb perfusion; L-PAM, melphalan; PR, partial response; R0, R1, R2, radicality of resection; RT, radiotherapy; SD, stable disease.

Figure 2. Local progression-free survival according to HILP drug schedule. HILP, hyperthermic isolated limb perfusion; L-PAM, melphalan; LPFS, local progression-free survival.