Lejeune F J, Pujol N, Liénard D, Mosimann F, Raffoul W, Genton A, Guillou L, Landry M, Chassot P G, Chiolero R, Bischof-Delaloye A, Leyvraz S, Mirimanoff R O, Bejkos D, Leyvraz P F
Multidisciplinary Oncology Centre, and Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Eur J Surg Oncol. 2000 Nov;26(7):669-78. doi: 10.1053/ejso.2000.0979.
Patients with non-resectable soft tissue sarcomas of the extremities do not live longer if they are treated by amputation or disarticulation. In order to avoid major amputations, we tested isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF)+melphalan+/-interferon-gamma (IFN) as a pre-operative, neoadjuvant limb salvage treatment.
Twenty-two patients were included (six men and 16 women; three upper limb and 19 lower limb tumours). The AJCC stage was IIA in four patients, III in seven and IV in 11. Thirteen cases were recurrent or progressive after previous therapy; five tumours had a diameter >/=20 cm, and four were multiple or regionally metastatic. There were six malignant fibrous histiocytomas, five liposarcomas, four malignant peripheral nerve sheath tumours, three rhabdomyosarcomas, two leiomyosarcomas, one recurrent extraskeletal osteosarcoma and one angiosarcoma.
Twenty-four ILPs were performed in the 22 patients, and 18 (82%) experienced an objective response: this was complete in four (18%) and partial in 14 (64%). Three patients had a minimal or no response and the tumour progressed in one case. All patients had fever for 24 hours but only one developed a reversible grade 3 distributive shock syndrome with no sequelae. There was no grade 4 toxicity. Seventeen patients (77%) underwent limb-sparing resection of the tumour remnants after a median time of 3.4 months: 10 resections were intracompartmental and seven extracompartmental. Surgery included flaps or skin grafts in five patients, arterial replacement in two and knee arthrodesis in one. Adjuvant chemotherapy was given to eight patients and radiotherapy to six. In one patient amputation was necessary after a second ILP. Secondary amputations were performed for recurrence in two patients, resulting in an overall limb salvage rate of 19/22 (86%). After a median follow-up of 18.7 months, 10 recurrences were recorded: seven were both local and systemic and three were only local. The median disease free and overall survival times have been >12.5 and 18.7 months respectively: this is similar to the outcome after primary amputations for similar cases.
ILP with TNF and chemotherapy is an efficient limb sparing neoadjuvant therapy for a priori non-resectable limb soft tissue sarcomas.
对于肢体不可切除的软组织肉瘤患者，截肢或关节离断术并不能延长其生存期。为避免大截肢，我们测试了以肿瘤坏死因子α（TNF）+美法仑±干扰素-γ（IFN）进行孤立肢体灌注（ILP）作为术前新辅助保肢治疗。
纳入22例患者（6例男性和16例女性；3例上肢肿瘤和19例下肢肿瘤）。美国癌症联合委员会（AJCC）分期为IIA期4例，III期7例，IV期11例。13例患者在先前治疗后复发或病情进展；5个肿瘤直径≥20 cm，4个为多发或区域转移。其中有6例恶性纤维组织细胞瘤、5例脂肪肉瘤、4例恶性外周神经鞘瘤、3例横纹肌肉瘤、2例平滑肌肉瘤、1例复发性骨外骨肉瘤和1例血管肉瘤。
22例患者共进行了24次ILP，18例（82%）出现客观缓解：4例（18%）完全缓解，14例（64%）部分缓解。3例患者缓解轻微或无缓解，1例患者肿瘤进展。所有患者均发热24小时，但仅1例发生可逆性3级分布性休克综合征，无后遗症。无4级毒性反应。17例患者（77%）在中位时间3.4个月后对肿瘤残余进行了保肢切除：10例为骨内切除，7例为骨外切除。手术包括5例患者的皮瓣或植皮、2例患者的动脉置换和1例患者的膝关节融合术。8例患者接受辅助化疗，6例接受放疗。1例患者在第二次ILP后需要截肢。2例患者因复发进行了二次截肢，总体保肢率为19/22（86%）。中位随访18.7个月后，记录到10例复发：7例为局部和全身复发，3例仅为局部复发。无病生存期和总生存期的中位数分别>12.5个月和18.7个月：这与类似病例初次截肢后的结果相似。
TNF联合化疗的ILP是一种有效的保肢新辅助治疗方法，适用于先前所认为的不可切除的肢体软组织肉瘤。
