melphalan and Liposarcoma

The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible.. To increase the number of limb-sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation.. In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon-tau. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP.. A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow-up of almost 2 years (22 months; range, 6-58 months), limb salvage was achieved in 82%. Regional toxicity was limited and systemic toxicity minimal to moderate, easily managed, with no toxic deaths.. In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Histiocytoma, Benign Fibrous; Humans; Liposarcoma; Male; Melphalan; Middle Aged; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha

Tumor necrosis factor alpha (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is one of the most effective treatment modalities for unresectable soft tissue sarcoma (STS) of the extremities. Liposarcomas (LS) are a large and heterogeneous subgroup of STS with different biological behavior and prognoses. The aim of this study was to evaluate LS and the different subentities with respect to their responsiveness towards TM-ILP.. We matched our ILP database with our pathology database to identify patients who received TM-ILP due to STS followed by resection of the residual tumor. We identified 126 patients who matched these inclusion criteria. In this patient group we identified 24 patients with a LS. Histopathological regression was assessed from all resection specimens and was compared between groups: LS vs. non-LS and for myxoid and non-myxoid LS subgroups.. There were no significant differences in the overall tumor regression comparing non-LS (median 95%, mean 77%) and LS (median 90%, mean 74%). For the subgroup analysis, a higher grade of regression after TM-ILP was found in myxoid-LS (median 95%, mean 79% ± 31.5) compared to the non-myxoid LS (median 75%, mean 72% ± 24.6). Atypical lipomatous tumors (ALT) were less responsive to TM-ILP treatment (median 40%, mean 40%).. The histopathological response of LS toward TM-ILP is equally good compared to non-lipomatous STS. Myxoid LS seem to have a tendency towards a better response to TM-ILP compared to non-myxoid LS and ALT showed the lowest response rate in the liposarcoma subgroup. Furthermore, we found that TM-ILP seems to facilitate successful R0 resection. Due to the low number of cases in the subgroups we advocate further research on this topic.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Humans; Liposarcoma; Male; Melphalan; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm, Residual; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF alpha) +/-interferon gamma (IFN gamma) and melphalan in patients with primarily irresectable soft tissue sarcoma is promising in terms of tumor regression and limb salvage. However, the feasibility of radiotherapy in combination with this treatment modality has not been established.. Fifteen patients with irresectable soft tissue tumors of the limb underwent ILP with TNF alpha, +/-IFN gamma, and melphalan. Three groups could be distinguished with respect to the role of radiotherapy. In nine patients, the residual tumor could be resected after ILP, and this was followed by radiotherapy with a total dose of 50-70 Gy (2 Gy/day). In one patient with aggressive fibromatosis, ILP was followed by radiotherapy without tumor resection (Group I). In two patients who underwent ILP for recurrent sarcoma, the primary tumor had been treated before by resection and radiotherapy (60 Gy) (Group II). In three patients whose tumors remained irresectable after ILP, radiotherapy was applied later in the course of disease for local palliation (Group III).. In Group I, healing of the resection wound was markedly delayed in four patients, with soft tissue necrosis and infection necessitating amputation in two of them. Following completion of radiotherapy, persistent lymphoceles were encountered in two patients. Radiotherapy-induced fibrosis was encountered in five patients, resulting in a mild limb malfunction in two. Three-patients developed mild edema during radiotherapy. Tumor-associated neuropathy was aggravated by ILP in three patients causing severely disabling motor deficits and limb contractures in two of them. In Group II, ILP did not cause any local problem in the heavily irradiated areas. In Group III, pre-existing limb edema was increased after a total palliative dose of 20 Gy in one patient. Another patient, who had been re-operated for arterial thrombosis immediately after ILP, developed occlusion of the brachial artery 4 months after completion of palliative radiotherapy (36 Gy in 6 Gy fractions).. In patients with irresectable soft tissue tumors, multimodality treatment using ILP with TNF alpha +/- IFN gamma and melphalan, tumor resection, and postoperative high-dose radiotherapy is associated with a considerable risk of tissue necrosis and impaired healing. This risk should be weighed against a possible benefit from radiotherapy in local tumor control.

Topics: Adult; Aged; Antineoplastic Agents; Arm; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Edema; Female; Humans; Interferon-gamma; Leg; Liposarcoma; Male; Melphalan; Middle Aged; Necrosis; Radiation Injuries; Radiotherapy Dosage; Retrospective Studies; Risk; Sarcoma; Skin; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan.. PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor.. FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

Topics: Chemotherapy, Cancer, Regional Perfusion; Contrast Media; Deoxyglucose; Fluorodeoxyglucose F18; Humans; Interferon-gamma; Leg; Liposarcoma; Male; Melphalan; Middle Aged; Soft Tissue Neoplasms; Tomography, Emission-Computed; Tumor Necrosis Factor-alpha

Topics: Aged; Amputation, Surgical; Arm; Bone Neoplasms; Cartilage; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Female; Fibrosarcoma; Hemangiosarcoma; Humans; Leg; Liposarcoma; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Sarcoma

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Fibrosarcoma; Hemangiosarcoma; Humans; Leiomyosarcoma; Liposarcoma; Male; Melphalan; Neoplasm Metastasis; Neurilemmoma; Nitrogen Mustard Compounds; Sarcoma; Sarcoma, Synovial; Thiotepa

Topics: Aorta; Aorta, Abdominal; Bone Neoplasms; Carotid Arteries; Chemotherapy, Cancer, Regional Perfusion; Chondrosarcoma; Dactinomycin; Dogs; Fibrosarcoma; Iliac Artery; Iliac Vein; Leiomyosarcoma; Liposarcoma; Lymphoma, Non-Hodgkin; Melphalan; Mesothelioma; Neoplasms; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Kaposi; Subclavian Artery; Vena Cava, Inferior