TNF dose reduction and shortening of duration of isolated limb perfusion for locally advanced soft tissue sarcoma of the extremities is safe and effective in terms of long‐term patient outcome

Hoven-Gondrie, Miriam L.; Bastiaannet, E.; Ginkel, Robert J. van; Suurmeijer, Albert; Hoekstra, Harald J.

doi:10.1002/jso.21885

Cited by 34 publications

(15 citation statements)

References 49 publications

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“…In cases of small lesions restricted to the distal parts of the limb, isolated limb infusion with melphalan can be of value 36. Literature suggests that reduction of duration of TM-ILP has no influence on either clinical response or local control 37. However, these results are achieved in soft tissue sarcoma patients and should be investigated in an IT-mets melanoma study population.…”

Section: Discussionmentioning

confidence: 99%

20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters

et al. 2011

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BackgroundApproximately 5–8% of melanoma patients will develop in-transit metastases (IT-mets). Tumor necrosis factor-α (TNF) and melphalan-based isolated limb perfusion (TM-ILP) is an attractive treatment modality in melanoma patients with multiple IT-mets. This study reports on a 20 years experience and outlines the evolution and major changes since the introduction of TNF in ILP.MethodsA total of 167 TM-ILPs were performed in 148 patients, between 1991 and 2009. TM-ILPs were performed at high doses of TNF (3–4 mg) from 1991 to 2004 (n = 99) and at low doses of TNF (1–2 mg) from 2004 to 2009 (n = 68) under mild hyperthermic conditions (38°C–39.5°C.). Melphalan doses were unchanged at 10–13 mg/l (leg and arm, respectively). Characteristics for the 167 ILPs were: 81 stage IIIB, 65 stage IIIC, and 21 stage IV disease.ResultsThe overall response rate was 89% (n = 148). (Complete response [CR] = 61%; partial response [PR] = 28%). CR rates correlated with stage (P = .001) and with high-dose vs. low-dose TNF (70% vs. 49%; P < .006). High-dose TNF prolonged local control (median 16 months vs. 11 months; P = .076). Survival was not influenced by TNF dose. CR after ILP and number of lesions also correlated with local progression-free interval. Overall survival did correlate with stage of disease (P < .001), size of the lesions (P = .001), and a CR (P < .001).ConclusionsThis 2-decade single-center experience demonstrates that TM-ILP is a safe and effective treatment modality for melanoma patients with multiple IT-mets. Higher dose of TNF was associated with significantly higher CR rates and prolonged local control without an effect on overall survival.

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Section: Discussionmentioning

confidence: 99%

20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters

et al. 2011

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“…Remarkably, tumor surgery was performed as a shelling‐out procedure with R2 resections in a relevant number of patients. The results at Groningen for 71 patients were much better, with an estimated 5‐year LDFS of 87% achieved by compartment‐oriented resection of the residual tumor . With a similar surgical approach, the estimated 5‐year LDFS was 82% for 90 patients treated at the sarcoma centers of Berlin and Mannheim with TNF‐ILP as a neoadjuvant treatment followed by radical limb‐preserving resection, and the estimated 5‐year metastasis‐free survival rate was 51%, which demonstrated the aggressive behavior of the sarcomas selected for ILP treatment .…”

Section: Oncological Outcome After Tnf‐ilp and Tumor Resectionmentioning

confidence: 94%

“…Currently, most ILP centers do not use rhTNFα dosages greater than 2 mg for the lower extremities or greater than 1 mg for the upper extremities. In the initial trials, melphalan was injected into the limb circuit 30 minutes after rhTNFα, and the cumulative perfusion time was 90 minutes . Hoven‐Gondri et al demonstrated that the perfusion time may be reduced to 60 minutes without the treatment response being compromised. The standard perfusion time is currently 60 to 75 minutes, and melphalan is administered 15 minutes after rhTNFα. The vascular access for establishing the limb circuit is chosen to be as close to the tumor as possible.…”

Section: Current Standards In Tnf‐ilpmentioning

confidence: 99%

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Jakob

Hohenberger

2016

Cancer

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Isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan (TNF-ILP) is a highly effective regional treatment for locally advanced soft tissue sarcoma. This review critically discusses the indication for TNF-ILP. AbstractManagement of locally advanced extremity soft tissue sarcoma of the limbs is challenging particularly in recurrent tumors and those adjacent to neurovascular bundles and joints. Typically the tumors are large, below the fascia and of high grade (T2b, stage III according to AJCC) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics.Isolated limb perfusion with recombinant human tumor necrosis factor α (TNF-ILP) adds a therapeutic option to radiation therapy and systemic chemotherapy. Although the procedure is somewhat sophisticated to learn, it is a safe method working for now almost two decades in more than 50 centers worldwide. TNF-ILP yields a high rate of pathologic complete or near-complete tumor remission. Combined with post-ILP surgical resection of the tumor remnant the limb salvage rate is close to 90%. Often adjuvant radiation therapy can be spared without compromising longterm local tumor control rates. Nevertheless, TNF-ILP has never been compared to other treatment regimen in a randomized trial. This review summarizes the mode of action and the standard application of TNF-ILP and focuses on a critical discussion on the role of TNF-ILP in multimodal treatment of locally advanced primary and recurrent extremity sarcoma.

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“…First, the addition of postoperative EBRT to HILP and delayed surgical resection resulted in a significant improvement in local control without increasing morbidity in ESTS patients . Moreover, a follow‐up study showed that dose reduction and a shorter HILP duration was safe and effective for patient outcome, as the 5‐year local control rates and (limb) survival were not compromised …”

Section: Discussionmentioning

confidence: 99%

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas

Stevenson

Seinen

Pras

et al. 2018

Journal of Surgical Oncology

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TNF dose reduction and shortening of duration of isolated limb perfusion for locally advanced soft tissue sarcoma of the extremities is safe and effective in terms of long‐term patient outcome

Abstract: Dose reduction and shorter duration of TM-ILP seem to be safe and effective regarding long-term patient outcome, as 5-year local control rates and (limb)-survival are not compromised.

Cited by 34 publications

References 49 publications

20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters

20 Years Experience of TNF-Based Isolated Limb Perfusion for In-Transit Melanoma Metastases: TNF Dose Matters

Role of isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan in locally advanced extremity soft tissue sarcoma

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas

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